News Reader.info

ABSTRACT Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens,

amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show

that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression,

methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and

susceptibility to neurological disorders. This set of genes is significantly enriched for _Drosophila_ orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily

conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease. Access through your institution Buy or subscribe This is a

preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value

online-access subscription $32.99 / 30 days cancel any time Learn more Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more

Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS:

* Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS GENOMIC ANALYSIS OF INTRACRANIAL AND SUBCORTICAL BRAIN

VOLUMES YIELDS POLYGENIC SCORES ACCOUNTING FOR VARIATION ACROSS ANCESTRIES Article 21 October 2024 GENOME-WIDE ASSOCIATION STUDY OF CEREBELLAR VOLUME PROVIDES INSIGHTS INTO HERITABLE

MECHANISMS UNDERLYING BRAIN DEVELOPMENT AND MENTAL HEALTH Article Open access 16 July 2022 THE GENETIC ARCHITECTURE OF HUMAN BRAINSTEM STRUCTURES AND THEIR INVOLVEMENT IN COMMON BRAIN

DISORDERS Article Open access 11 August 2020 DATA AVAILABILITY The genome-wide summary statistics that support the findings of this study are available from the CHARGE dbGaP (accession code:

phs000930) and ENIGMA (http://enigma.ini.usc.edu/research/download-enigma-gwas-results) websites. REFERENCES * Marsden, C. D. The mysterious motor function of the basal ganglia: the Robert

Wartenberg Lecture. _Neurology_ 32, 514–539 (1982). Article  CAS  PubMed  Google Scholar  * Yin, H. H. & Knowlton, B. J. The role of the basal ganglia in habit formation. _Nat. Rev.

Neurosci._ 7, 464–476 (2006). Article  CAS  PubMed  Google Scholar  * McDonald, A. J. & Mott, D. D. Functional neuroanatomy of amygdalohippocampal interconnections and their role in

learning and memory. _J. Neurosci. Res._ 95, 797–820 (2016). Article  PubMed  PubMed Central  CAS  Google Scholar  * Hikosaka, O., Kim, H. F., Yasuda, M. & Yamamoto, S. Basal ganglia

circuits for reward value-guided behavior. _Annu. Rev. Neurosci._ 37, 289–306 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Salzman, C. D. & Fusi, S. Emotion,

cognition, and mental state representation in amygdala and prefrontal cortex. _Annu. Rev. Neurosci._ 33, 173–202 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Floresco, S.

B. The nucleus accumbens: an interface between cognition, emotion, and action. _Annu. Rev. Psychol._ 66, 25–52 (2015). Article  PubMed  Google Scholar  * Fabbro, F., Aglioti, S. M.,

Bergamasco, M., Clarici, A. & Panksepp, J. Evolutionary aspects of self- and world consciousness in vertebrates. _Front. Hum. Neurosci._ 9, 157 (2015). Article  PubMed  PubMed Central 

Google Scholar  * Alexander, G. E., DeLong, M. R. & Strick, P. L. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. _Annu. Rev. Neurosci._ 9,

357–381 (1986). Article  CAS  PubMed  Google Scholar  * Jahanshahi, M., Obeso, I., Rothwell, J. C. & Obeso, J. A. A fronto–striato–subthalamic–pallidal network for goal-directed and

habitual inhibition. _Nat. Rev. Neurosci._ 16, 719–732 (2015). Article  CAS  PubMed  Google Scholar  * Shepherd, G. M. Corticostriatal connectivity and its role in disease. _Nat. Rev.

Neurosci._ 14, 278–291 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * Stratmann, K. et al. Precortical phase of Alzheimer’s disease (AD)-related Tau cytoskeletal pathology.

_Brain Pathol._ 26, 371–386 (2016). Article  CAS  PubMed  Google Scholar  * Del Tredici, K., Rub, U., De Vos, R. A., Bohl, J. R. & Braak, H. Where does Parkinson disease pathology begin

in the brain? _J. Neuropathol. Exp. Neurol._ 61, 413–426 (2002). Article  PubMed  Google Scholar  * Hibar, D. P. et al. Common genetic variants influence human subcortical brain structures.

_Nature_ 520, 224–229 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Elliott, L. T. et al. Genome-wide association studies of brain imaging phenotypes in UK Biobank.

_Nature_ 562, 210–216 (2018). Article  CAS  PubMed  PubMed Central  Google Scholar  * Renteria, M. E. et al. Genetic architecture of subcortical brain regions: common and region-specific

genetic contributions. _Genes Brain Behav._ 13, 821–830 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Clarke, L. et al. The 1000 Genomes Project: data management and

community access. _Nat. Methods_ 9, 459–462 (2012). Article  CAS  PubMed  PubMed Central  Google Scholar  * McCarthy, S. et al. A reference panel of 64,976 haplotypes for genotype

imputation. _Nat. Genet._ 48, 1279–1283 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Willer, C. J., Li, Y. & Abecasis, G. R. METAL: fast and efficient meta-analysis of

genomewide association scans. _Bioinformatics_ 26, 2190–2191 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Pruim, R. J. et al. LocusZoom: regional visualization of

genome-wide association scan results. _Bioinformatics_ 26, 2336–2337 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Hibar, D. P. et al. Novel genetic loci associated with

hippocampal volume. _Nat. Commun._ 8, 13624 (2017). Article  CAS  PubMed  PubMed Central  Google Scholar  * Adams, H. H. et al. Novel genetic loci underlying human intracranial volume

identified through genome-wide association. _Nat. Neurosci._ 19, 1569–1582 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Verhaaren, B. F. et al. Multiethnic genome-wide

association study of cerebral white matter hyperintensities on MRI. _Circ. Cardiovasc. Genet._ 8, 398–409 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Malik, R. et al.

Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. _Nat. Genet._ 50, 524–537 (2018). Article  CAS  PubMed  PubMed

Central  Google Scholar  * Yengo, L. et al. Meta-analysis of genome-wide association studies for height and body mass index in approximately 700000 individuals of European ancestry. _Hum.

Mol. Genet._ 27, 3641–3649 (2018). Article  CAS  PubMed  PubMed Central  Google Scholar  * Davies, G. et al. Study of 300,486 individuals identifies 148 independent genetic loci influencing

general cognitive function. _Nat. Commun._ 9, 2098 (2018). Article  PubMed  PubMed Central  CAS  Google Scholar  * Kunkle, B. W. et al. Genetic meta-analysis of diagnosed Alzheimer’s disease

identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. _Nat. Genet._ 51, 414–430 (2019). Article  CAS  PubMed  PubMed Central  Google Scholar  * Simon-Sanchez, J.

et al. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. _Nat. Genet._ 41, 1308–1312 (2009). Article  CAS  PubMed  PubMed Central  Google Scholar  * Bipolar

Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium. Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes. _Cell_ 173,

1705–1715.e16 (2018). * Demontis, D. et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. _Nat. Genet._ 51, 63–75 (2019). Article 

CAS  PubMed  Google Scholar  * Finucane, H. K. et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. _Nat. Genet._ 47, 1228–1235 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar  * Hnisz, D. et al. Super-enhancers in the control of cell identity and disease. _Cell_ 155, 934–947 (2013). Article  CAS  PubMed 

Google Scholar  * Szklarczyk, D. et al. STRINGv10: protein–protein interaction networks, integrated over the tree of life. _Nucleic Acids Res._ 43, D447–D452 (2015). Article  CAS  PubMed 

Google Scholar  * Deans, M. R. et al. Control of neuronal morphology by the atypical cadherin Fat3. _Neuron_ 71, 820–832 (2011). Article  CAS  PubMed  PubMed Central  Google Scholar  *

Takahashi, K. et al. Expression of _FOXP2_ in the developing monkey forebrain: comparison with the expression of the genes _FOXP1_, _PBX3_, and _MEIS2_. _J. Comp. Neurol._ 509, 180–189

(2008). Article  CAS  PubMed  Google Scholar  * Kjaer-Sorensen, K. et al. Pregnancy-associated plasma protein A (PAPP-A) modulates the early developmental rate in zebrafish independently of

its proteolytic activity. _J. Biol. Chem._ 288, 9982–9992 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * Bayes-Genis, A. et al. Pregnancy-associated plasma protein A as a

marker of acute coronary syndromes. _N. Engl. J. Med._ 345, 1022–1029 (2001). Article  CAS  PubMed  Google Scholar  * Funayama, A. et al. Serum pregnancy-associated plasma protein A in

patients with heart failure. _J. Card. Fail._ 17, 819–826 (2011). Article  CAS  PubMed  Google Scholar  * Desbuquois, B., Carre, N. & Burnol, A. F. Regulation of insulin and type 1

insulin-like growth factor signaling and action by the Grb10/14 and SH2B1/B2 adaptor proteins. _FEBS J._ 280, 794–816 (2013). CAS  PubMed  Google Scholar  * Li, J. et al. TXNDC5 contributes

to rheumatoid arthritis by down-regulating IGFBP1 expression. _Clin. Exp. Immunol._ 192, 82–94 (2018). Article  CAS  PubMed  Google Scholar  * Matulka, K. et al. PTP1B is an effector of

activin signaling and regulates neural specification of embryonic stem cells. _Cell Stem Cell_ 13, 706–719 (2013). Article  CAS  PubMed  Google Scholar  * Krishnan, N. et al. PTP1B

inhibition suggests a therapeutic strategy for Rett syndrome. _J. Clin. Invest._ 125, 3163–3177 (2015). Article  PubMed  PubMed Central  Google Scholar  * Sebastian-Serrano, A. et al.

Tissue-nonspecific alkaline phosphatase regulates purinergic transmission in the central nervous system during development and disease. _Comput. Struct. Biotechnol. J._ 13, 95–100 (2015).

Article  CAS  PubMed  Google Scholar  * Diaz-Hernandez, M. et al. Tissue-nonspecific alkaline phosphatase promotes the neurotoxicity effect of extracellular tau. _J. Biol. Chem._ 285,

32539–32548 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Vardy, E. R., Kellett, K. A., Cocklin, S. L. & Hooper, N. M. Alkaline phosphatase is increased in both brain

and plasma in Alzheimer’s disease. _Neurodegener. Dis._ 9, 31–37 (2012). Article  CAS  PubMed  Google Scholar  * Kellett, K. A., Williams, J., Vardy, E. R., Smith, A. D. & Hooper, N. M.

Plasma alkaline phosphatase is elevated in Alzheimer’s disease and inversely correlates with cognitive function. _Int. J. Mol. Epidemiol. Genet._ 2, 114–121 (2011). CAS  PubMed  PubMed

Central  Google Scholar  * Searles Quick, V. B., Davis, J. M., Olincy, A. & Sikela, J. M. DUF1220 copy number is associated with schizophrenia risk and severity: implications for

understanding autism and schizophrenia as related diseases. _Transl. Psychiatry_ 5, e697 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Hsu, S. C. et al. Mutations in

_SLC20A2_ are a major cause of familial idiopathic basal ganglia calcification. _Neurogenetics_ 14, 11–22 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * Taglia, I.,

Bonifati, V., Mignarri, A., Dotti, M. T. & Federico, A. Primary familial brain calcification: update on molecular genetics. _Neurol. Sci._ 36, 787–794 (2015). Article  PubMed  Google

Scholar  * Figueiro-Silva, J. et al. Neuronal pentraxin 1 negatively regulates excitatory synapse density and synaptic plasticity. _J. Neurosci._ 35, 5504–5521 (2015). Article  CAS  PubMed 

PubMed Central  Google Scholar  * Abad, M. A., Enguita, M., DeGregorio-Rocasolano, N., Ferrer, I. & Trullas, R. Neuronal pentraxin 1 contributes to the neuronal damage evoked by

amyloid-β and is overexpressed in dystrophic neurites in Alzheimer’s brain. _J. Neurosci._ 26, 12735–12747 (2006). Article  CAS  PubMed  PubMed Central  Google Scholar  * Tobaben, S.,

Varoqueaux, F., Brose, N., Stahl, B. & Meyer, G. A brain-specific isoform of small glutamine-rich tetratricopeptide repeat-containing protein binds to Hsc70 and the cysteine string

protein. _J. Biol. Chem._ 278, 38376–38383 (2003). Article  CAS  PubMed  Google Scholar  * Fonte, V. et al. Interaction of intracellular β amyloid peptide with chaperone proteins. _Proc.

Natl Acad. Sci. USA_ 99, 9439–9444 (2002). Article  CAS  PubMed  PubMed Central  Google Scholar  * Mao, C. X. et al. Microtubule-severing protein katanin regulates neuromuscular junction

development and dendritic elaboration in _Drosophila_. _Development_ 141, 1064–1074 (2014). Article  CAS  PubMed  Google Scholar  * Yu, W. et al. The microtubule-severing proteins spastin

and katanin participate differently in the formation of axonal branches. _Mol. Biol. Cell_ 19, 1485–1498 (2008). Article  CAS  PubMed  PubMed Central  Google Scholar  * Zhu, J., Shang, Y.

& Zhang, M. Mechanistic basis of MAGUK-organized complexes in synaptic development and signalling. _Nat. Rev. Neurosci._ 17, 209–223 (2016). Article  CAS  PubMed  Google Scholar  *

Ingason, A. et al. Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia. _Transl. Psychiatry_ 5, e656

(2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Nithianantharajah, J. et al. Synaptic scaffold evolution generated components of vertebrate cognitive complexity. _Nat.

Neurosci._ 16, 16–24 (2013). Article  CAS  PubMed  Google Scholar  * Nalls, M. A. et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for

Parkinson’s disease. _Nat. Genet._ 46, 989–993 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Guan, J. J. et al. DRAM1 regulates apoptosis through increasing protein levels

and lysosomal localization of BAX. _Cell Death Dis._ 6, e1624 (2015). Article  PubMed  PubMed Central  Google Scholar  * Yu, M., Jiang, Y., Feng, Q., Ouyang, Y. & Gan, J. DRAM1 protects

neuroblastoma cells from oxygen-glucose deprivation/reperfusion-induced injury via autophagy. _Int. J. Mol. Sci._ 15, 19253–19264 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar

  * Scarpa, J. R. et al. Systems genetic analyses highlight a TGFβ-FOXO3 dependent striatal astrocyte network conserved across species and associated with stress, sleep, and Huntington’s

disease. _PLoS Genet._ 12, e1006137 (2016). Article  PubMed  PubMed Central  CAS  Google Scholar  * Donlon, T. A. et al. FOXO3 longevity interactome on chromosome 6. _Aging Cell_ 16,

1016–1025 (2017). Article  CAS  PubMed  PubMed Central  Google Scholar  * Sears, J. C. & Broihier, H. T. FoxO regulates microtubule dynamics and polarity to promote dendrite branching in

_Drosophila_ sensory neurons. _Dev. Biol._ 418, 40–54 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Peng, K. et al. Knockdown of FoxO3a induces increased neuronal

apoptosis during embryonic development in zebrafish. _Neurosci. Lett._ 484, 98–103 (2010). Article  CAS  PubMed  Google Scholar  * Santama, N., Er, C. P., Ong, L. L. & Yu, H.

Distribution and functions of kinectin isoforms. _J. Cell Sci._ 117, 4537–4549 (2004). Article  CAS  PubMed  Google Scholar  * Liu, X. A., Rizzo, V. & Puthanveettil, S. V. Pathologies of

axonal transport in neurodegenerative diseases. _Transl. Neurosci._ 3, 355–372 (2012). Article  PubMed  Google Scholar  * Consortium, E. et al. Genome-wide association analysis of genetic

generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32. _Hum. Mol. Genet._ 21, 5359–5372 (2012). Article  CAS  Google Scholar  * Martins-de-Souza, D. et

al. Proteomic analysis identifies dysfunction in cellular transport, energy, and protein metabolism in different brain regions of atypical frontotemporal lobar degeneration. _J. Proteome

Res._ 11, 2533–2543 (2012). Article  CAS  PubMed  Google Scholar  * Shulman, J. M. et al. Functional screening in _Drosophila_ identifies Alzheimer’s disease susceptibility genes and

implicates Tau-mediated mechanisms. _Hum. Mol. Genet._ 23, 870–877 (2014). Article  CAS  PubMed  Google Scholar  * Friede, R. L. & Samorajski, T. Axon caliber related to neurofilaments

and microtubules in sciatic nerve fibers of rats and mice. _Anat. Rec._ 167, 379–387 (1970). Article  CAS  PubMed  Google Scholar  * Yuan, A., Rao, M. V., Veeranna & Nixon, R. A.

Neurofilaments and neurofilament proteins in health and disease. _Cold Spring Harb. Perspect. Biol._ 9, a018309 (2017). Article  PubMed  PubMed Central  CAS  Google Scholar  * Bis, J. C. et

al. Whole exome sequencing study identifies novel rare and common Alzheimer’s-associated variants involved in immune response and transcriptional regulation. _Mol Psychiatry_

https://doi.org/10.1038/s41380-018-0112-7 (2018). * Marioni, R. E. et al. GWAS on family history of Alzheimer’s disease. _Transl. Psychiatry_ 8, 99 (2018). Article  PubMed  PubMed Central 

Google Scholar  * Psaty, B. M. et al. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: design of prospective meta-analyses of genome-wide association studies

from 5 cohorts. _Circ. Cardiovasc. Genet._ 2, 73–80 (2009). Article  PubMed  PubMed Central  Google Scholar  * Thompson, P. M. et al. The ENIGMA Consortium: large-scale collaborative

analyses of neuroimaging and genetic data. _Brain Imaging Behav._ 8, 153–182 (2014). Article  PubMed  PubMed Central  Google Scholar  * Sudlow, C. et al. UK Biobank: an open access resource

for identifying the causes of a wide range of complex diseases of middle and old age. _PLoS Med._ 12, e1001779 (2015). Article  PubMed  PubMed Central  Google Scholar  * Tsao, C. W. &

Vasan, R. S. Cohort Profile: the Framingham Heart Study (FHS): overview of milestones in cardiovascular epidemiology. _Int. J. Epidemiol._ 44, 1800–1813 (2015). Article  PubMed  PubMed

Central  Google Scholar  * Schmidt, R. et al. Assessment of cerebrovascular risk profiles in healthy persons: definition of research goals and the Austrian Stroke Prevention Study (ASPS).

_Neuroepidemiology_ 13, 308–313 (1994). Article  CAS  PubMed  Google Scholar  * Almasy, L. & Blangero, J. Multipoint quantitative-trait linkage analysis in general pedigrees. _Am. J.

Hum. Genet._ 62, 1198–1211 (1998). Article  CAS  PubMed  PubMed Central  Google Scholar  * Yang, J., Lee, S. H., Goddard, M. E. & Visscher, P. M. GCTA: a tool for genome-wide complex

trait analysis. _Am. J. Hum. Genet._ 88, 76–82 (2011). Article  CAS  PubMed  PubMed Central  Google Scholar  * Bulik-Sullivan, B. K. et al. LD score regression distinguishes confounding from

polygenicity in genome-wide association studies. _Nat. Genet._ 47, 291–295 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Winkler, T. W. et al. Quality control and conduct

of genome-wide association meta-analyses. _Nat. Protoc._ 9, 1192–1212 (2014). Article  PubMed  PubMed Central  Google Scholar  * Bennett, D. A., Yu, L. & De Jager, P. L. Building a

pipeline to discover and validate novel therapeutic targets and lead compounds for Alzheimer’s disease. _Biochem. Pharm._ 88, 617–630 (2014). Article  CAS  PubMed  Google Scholar  * Chan, G.

et al. _CD33_ modulates TREM2: convergence of Alzheimer loci. _Nat. Neurosci._ 18, 1556–1558 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Johnson, W. E., Li, C. &

Rabinovic, A. Adjusting batch effects in microarray expression data using empirical Bayes methods. _Biostatistics_ 8, 118–127 (2007). Article  PubMed  Google Scholar  * Roadmap Epigenomics

Association et al. Integrative analysis of 111 reference human epigenomes. _Nature_ 518, 317–330 (2015). Article  CAS  Google Scholar  * Eicher, J. D. et al. GRASPv2.0: an update on the

Genome-Wide Repository of Associations between SNPs and phenotypes. _Nucleic Acids Res._ 43, D799–D804 (2015). Article  CAS  PubMed  Google Scholar  * Zhang, X. et al. Synthesis of 53 tissue

and cell line expression QTL datasets reveals master eQTLs. _BMC Genomics_ 15, 532 (2014). Article  PubMed  PubMed Central  CAS  Google Scholar  * Zhang, W. et al. SCAN database:

facilitating integrative analyses of cytosine modification and expression QTL. _Database_ 2015, bav025 (2015). Article  PubMed  PubMed Central  CAS  Google Scholar  * Consortium, G. T. The

Genotype-Tissue Expression (GTEx) project. _Nat. Genet._ 45, 580–585 (2013). Article  CAS  Google Scholar  * Veyrieras, J. B. et al. High-resolution mapping of expression-QTLs yields insight

into human gene regulation. _PLoS Genet._ 4, e1000214 (2008). Article  PubMed  PubMed Central  CAS  Google Scholar  * Bennett, D. A. et al. Overview and findings from the rush Memory and

Aging Project. _Curr. Alzheimer Res._ 9, 646–663 (2012). Article  CAS  PubMed  PubMed Central  Google Scholar  * Bennett, D. A., Schneider, J. A., Arvanitakis, Z. & Wilson, R. S.

Overview and findings from the religious orders study. _Curr. Alzheimer Res._ 9, 628–645 (2012). Article  CAS  PubMed  PubMed Central  Google Scholar  * Replogle, J. M. et al. A TREM1

variant alters the accumulation of Alzheimer-related amyloid pathology. _Ann. Neurol._ 77, 469–477 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Barnes, L. L., Schneider,

J. A., Boyle, P. A., Bienias, J. L. & Bennett, D. A. Memory complaints are related to Alzheimer disease pathology in older persons. _Neurology_ 67, 1581–1585 (2006). Article  CAS  PubMed

  Google Scholar  * McKeith, I. G. et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International

Workshop. _Neurology_ 47, 1113–1124 (1996). Article  CAS  PubMed  Google Scholar  * Schneider, J. A. et al. Substantia nigra tangles are related to gait impairment in older persons. _Ann.

Neurol._ 59, 166–173 (2006). Article  PubMed  Google Scholar  * Zheng, J. et al. LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential

of summary level GWAS data for SNP heritability and genetic correlation analysis. _Bioinformatics_ 33, 272–279 (2017). Article  CAS  PubMed  Google Scholar  * Wangler, M. F., Hu, Y. &

Shulman, J. M. _Drosophila_ and genome-wide association studies: a review and resource for the functional dissection of human complex traits. _Dis. Model Mech._ 10, 77–88 (2017). Article 

CAS  PubMed  PubMed Central  Google Scholar  * Hu, Y. et al. An integrative approach to ortholog prediction for disease-focused and other functional studies. _BMC Bioinformatics_ 12, 357

(2011). Article  PubMed  PubMed Central  Google Scholar  * Marygold, S. J., Crosby, M. A., Goodman, J. L. & FlyBase, C. Using FlyBase, a database of _Drosophila_ genes and genomes.

_Methods Mol. Biol._ 1478, 1–31 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We thank all of the study participants for contributing to

this research. Full acknowledgements and grant support details are provided in the Supplementary Note. AUTHOR INFORMATION Author notes * These authors contributed equally: Claudia L.

Satizabal, Hieab H. H. Adams, Derrek P. Hibar, Charles C. White. * These authors jointly supervised this work: Sarah E. Medland, Joshua M. Shulman, Paul M. Thompson, Sudha Seshadri, M. Arfan

Ikram. AUTHORS AND AFFILIATIONS * Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA Claudia L. Satizabal * Department of

Population Health Sciences, UT Health San Antonio, San Antonio, TX, USA Claudia L. Satizabal * The Framingham Heart Study, Framingham, MA, USA Claudia L. Satizabal, Jayandra J. Himali, 

Honghuang Lin, Alexa S. Beiser, Anita L. DeStefano & Sudha Seshadri * Department of Neurology, Boston University School of Medicine, Boston, MA, USA Claudia L. Satizabal, Jayandra J.

Himali, Alexa S. Beiser, Stéphanie Debette & Sudha Seshadri * Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands Hieab H. H. Adams, Maria J. Knol, Gennady V. Roshchupkin,

 Sven J. van der Lee, Meike W. Vernooij, Najaf Amin, Albert Hofman, André G. Uitterlinden, M. Kamran Ikram, Cornelia M. van Duijn & M. Arfan Ikram * Department of Radiology and Nuclear

Medicine, Erasmus MC, Rotterdam, the Netherlands Hieab H. H. Adams, Gennady V. Roshchupkin, Meike W. Vernooij, Wiro J. Niessen, Tonya White & M. Arfan Ikram * Department of Clinical

Genetics, Erasmus MC, Rotterdam, the Netherlands Hieab H. H. Adams * Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine,

University of Southern California, Los Angeles, CA, USA Derrek P. Hibar, Jason L. Stein, Neda Jahanshad, Christopher R. K. Ching, Christopher D. Whelan, Joshua W. Cheung, Arvin Saremi & 

Paul M. Thompson * Cell Circuits Program, Broad Institute, Cambridge, MA, USA Charles C. White & Philip L. De Jager * Center for Translational and Computational Neuroimmunology,

Department of Neurology, Columbia University Medical Center, New York, NY, USA Charles C. White & Philip L. De Jager * Department of Genetics, University of North Carolina, Chapel Hill,

NC, USA Jason L. Stein * UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA Jason L. Stein * Institute for Medical Informatics, Statistics and Epidemiology,

University of Leipzig, Leipzig, Germany Markus Scholz & Markus Loeffler * LIFE: The Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany Markus

Scholz, Ralph Burkhardt, Markus Loeffler & Matthias L. Schroeter * University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Team VINTAGE, UMR 1219, Bordeaux, France

Muralidharan Sargurupremraj, Ganesh Chauhan & Stéphanie Debette * Department of Medical Informatics, Erasmus MC, Rotterdam, the Netherlands Gennady V. Roshchupkin & Wiro J. Niessen *

Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA Albert V. Smith * Faculty of Medicine, University of Iceland, Reykjavík, Iceland Albert V. Smith & Vilmundur

Gudnason * Icelandic Heart Association, Kopavogur, Iceland Albert V. Smith & Vilmundur Gudnason * Cardiovascular Health Research Unit, Department of Medicine, University of Washington,

Seattle, WA, USA Joshua C. Bis & Bruce M. Psaty * The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA Xueqiu Jian

 & Myriam Fornage * Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK Michelle Luciano, Saskia P. Hagenaars, David

C. M. Liewald, Andrew M. McIntosh, Ian J. Deary & Joanna M. Wardlaw * Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria Edith Hofer

 & Reinhold Schmidt * Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria Edith Hofer * Institute for Community Medicine,

University Medicine Greifswald, Greifswald, Germany Alexander Teumer & Henry Völzke * Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA Jingyun Yang, 

Konstantinos Arfanakis, Debra A. Fleischman & David A. Bennett * Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA Jingyun Yang, Debra A. Fleischman 

& David A. Bennett * GeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA Lisa R. Yanek, Diane M. Becker & Paul A.

Nyquist * Department of Neurology, Baylor College of Medicine, Houston, TX, USA Tom V. Lee & Joshua M. Shulman * Department of Biostatistics, Boston University School of Public Health,

Boston, MA, USA Shuo Li, Jayandra J. Himali, Qiong Yang, Alexa S. Beiser & Anita L. DeStefano * Department of Genetics, Harvard Medical School, Boston, MA, USA Yanhui Hu * Singapore Eye

Research Institute, Singapore National Eye Centre, Singapore, Singapore Jia Yu Koh, Ching-Yu Cheng & Tien Yin Wong * Division of Intramural Research, Population Sciences Branch, National

Heart, Lung and Blood Institute, Framingham, MA, USA John D. Eicher & Andrew D. Johnson * MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London,

London, UK Sylvane Desrivières, Tianye Jia, Christine Macare & Gunter Schumann * Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands

Alejandro Arias-Vasquez, Jennifer S. Richards, Daan van Rooij, Jan K. Buitelaar & Guillén Fernández * Department of Human Genetics, Radboud University Medical Center, Nijmegen, the

Netherlands Alejandro Arias-Vasquez, Janita Bralten, Martine Hoogman, Marieke Klein, Elena Shumskaya, Marjolein M. J. van Donkelaar, Thomas Wolfers, Hans van Bokhoven, Han G. Brunner & 

Barbara Franke * Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands Alejandro Arias-Vasquez, Nanda Rommelse & Barbara Franke * Donders Institute for

Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands Alejandro Arias-Vasquez, Janita Bralten, Martine Hoogman, Marieke Klein, Andre F. Marquand, Jennifer S.

Richards, Nanda Rommelse, Elena Shumskaya, Marjolein M. J. van Donkelaar, Daan van Rooij, Thomas Wolfers, Marcel P. Zwiers, Hans van Bokhoven, Han G. Brunner, Jan K. Buitelaar, Guillén

Fernández, Simon E. Fisher, Clyde Francks & Barbara Franke * Centre for Brain Research, Indian Institute of Science, Bangalore, India Ganesh Chauhan * CoE NORMENT, Division of Mental

Health and Addiction, Oslo University Hospital, Oslo, Norway Lavinia Athanasiu, Thomas Espeseth, Unn K. Haukvik, Lars T. Westlye, Dennis van der Meer, Ole A. Andreassen & Ingrid Melle *

CoE NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway Lavinia Athanasiu, Nhat Trung Doan, Ingrid Agartz, Lars T. Westlye, Dennis van der Meer, Erik G. Jönsson, Ole A.

Andreassen & Ingrid Melle * Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia Miguel E. Rentería * Center for

Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA Sungeun Kim & Kwangsik Nho * Center for Neuroimaging, Radiology and Imaging

Sciences, Indiana University School of Medicine, Indianapolis, IN, USA Sungeun Kim, Kwangsik Nho, Shannon L. Risacher & Andrew J. Saykin * Indiana Alzheimer Disease Center, Indiana

University School of Medicine, Indianapolis, IN, USA Sungeun Kim, Kwangsik Nho, Shannon L. Risacher, Tatiana M. Foroud & Andrew J. Saykin * Max Planck Institute of Psychiatry, Munich,

Germany David Hoehn, Nazanin Mirza-Schreiber, Benno Pütz, Philipp G. Sämann, Florian Holsboer & Bertram Müller-Myhsok * Mathematics and Statistics, Murdoch University, Perth, Western

Australia, Australia Nicola J. Armstrong * Lieber Institute for Brain Development, Baltimore, MD, USA Qiang Chen, Aaron L. Goldman, Venkata S. Mattay & Daniel R. Weinberger * Department

of Psychology, Yale University, New Haven, CT, USA Avram J. Holmes * Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA Avram J. Holmes, Stefan Ehrlich, Phil H. Lee, 

Randy L. Buckner, Joshua L. Roffman, Randy L. Gollub & Jordan W. Smoller * Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands Anouk den Braber,

 Dorret I. Boomsma, Eco J. C. de Geus, Jouke-Jan Hottenga, Iryna O. Fedko & Dennis van ‘t Ent * Netherlands Twin Register, Vrije Universiteit, Amsterdam, the Netherlands Anouk den

Braber, Dorret I. Boomsma, Eco J. C. de Geus, Jouke-Jan Hottenga, Iryna O. Fedko & Dennis van ‘t Ent * Amsterdam Neuroscience, Amsterdam, the Netherlands Anouk den Braber, Dorret I.

Boomsma, Eco J. C. de Geus, Jouke-Jan Hottenga & Dennis van ‘t Ent * Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, VU Amsterdam, Amsterdam UMC, Amsterdam,

the Netherlands Anouk den Braber * Medical University of Lodz, Lodz, Poland Iwona Kloszewska * Department of Integrative Medical Biology, Umeå University, Umeå, Sweden Micael Andersson &

 Lars Nyberg * Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden Micael Andersson & Lars Nyberg * Department of Psychology, University of Oslo, Oslo, Norway

Thomas Espeseth * Central Institute of Mental Health, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany Oliver Grimm, Andreas Meyer-Lindenberg & Marcella Rietschel *

Department of Psychiatry, UMC Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands Lucija Abramovic, Marc M. Bohlken, Marco P. Boks, Wiepke Cahn, 

Hilleke E. Hulshoff Pol, Rachel M. Brouwer, René S. Kahn & Neeltje E. M. van Haren * The Royal College of Surgeons in Ireland, Dublin, Ireland Saud Alhusaini, Norman Delanty & 

Christopher D. Whelan * Department of Neurology, Yale School of Medicine, New Haven, CT, USA Saud Alhusaini * Department of Psychiatry, Amsterdam Neuroscience, VU University Medical Center,

Amsterdam, the Netherlands Yuri Milaneschi, Brenda W. J. H. Penninx & Dick J. Veltman * Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK Martina

Papmeyer, Stephen M. Lawrie, Andrew M. McIntosh & Jessika E. Sussmann * Division of Systems Neuroscience of Psychopathology, Translational Research Center, University Hospital of

Psychiatry, University of Bern, Bern, Switzerland Martina Papmeyer * Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden

Tomas Axelsson * Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Dresden, Germany Stefan Ehrlich & Esther Walton *

Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA Stefan Ehrlich, Allison Stevens, Randy L. Gollub & Douglas N. Greve * Department of

Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander, Spain Roberto Roiz-Santiañez * Department of Medicine, University

Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria-IDIVAL, Santander, Spain Roberto Roiz-Santiañez & Benedicto Crespo-Facorro * Centro Investigación Biomédica en

Red Salud Mental, Santander, Spain Roberto Roiz-Santiañez, Diana Tordesillas-Gutierrez & Benedicto Crespo-Facorro * Section for Experimental Psychopathology and Neuroimaging, Department

of General Psychiatry, Heidelberg University, Heidelberg, Germany Bernd Kraemer & Oliver Gruber * Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and

Technology, Trondheim, Norway Asta K. Håberg * Department of Radiology, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway Asta K. Håberg * Centre for Academic Mental

Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK Hannah J. Jones * MRC Integrative Epidemiology Unit, Bristol Medical School, University of

Bristol, Bristol, UK Hannah J. Jones & George Davey Smith * NIHR Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol,

UK Hannah J. Jones * Department of Radiology, University of Calgary, Calgary, Alberta, Canada G. Bruce Pike * Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta,

Canada G. Bruce Pike * Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa Dan J. Stein, Jonathan C. Ipser, Nastassja Koen & Nynke A. Groenewold

* South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Cape Town, South Africa Dan J. Stein & Nastassja Koen * Laboratory of Epidemiology and

Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA Tamara B. Harris & Lenore J. Launer * INSERM, Research

Unit 1000 ‘Neuroimaging and Psychiatry’, Paris Saclay University and Paris Descartes University—DIGITEO Labs, Gif sur Yvette, France Irina Filippi, Hervé Lemaître & Jean-Luc Martinot *

Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany A. Veronica Witte, Shahrzad Kharabian Masouleh, Matthias L. Schroeter & Arno

Villringer * Faculty of Medicine, CRC 1052 ‘Obesity Mechanisms’, University of Leipzig, Leipzig, Germany A. Veronica Witte & Arno Villringer * International Max Planck Research School

for Language Sciences, Nijmegen, the Netherlands Tulio Guadalupe * Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands Tulio Guadalupe, 

Simon E. Fisher & Clyde Francks * Department of Psychiatry, University Medicine Greifswald, Greifswald, Germany Katharina Wittfeld, Deborah Janowitz & Hans J. Grabe * German Center

for Neurodegenerative Diseases, Greifswald, Germany Katharina Wittfeld, Wolfgang Hoffmann & Hans J. Grabe * Department of Medicine, University of Mississippi Medical Center, Jackson, MS,

USA Thomas H. Mosley * Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA James T. Becker * Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA James

T. Becker & Oscar L. Lopez * Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA James T. Becker & Oscar L. Lopez * Research Unit-Genetic Epidemiology, Gottfried

Schatz Research Centre for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria Yasaman Saba & Helena Schmidt * QIMR

Berghofer Medical Research Institute, Brisbane, Queensland, Australia Gabriel Cuellar-Partida, Lachlan T. Strike, Narelle K. Hansell, Nicholas G. Martin & Sarah E. Medland * Department

of Pharmacology, National University of Singapore, Singapore, Singapore Saima Hilal & Christopher Chen * Memory Aging and Cognition Center, National University Health System, Singapore,

Singapore Saima Hilal & Christopher Chen * Institute of Neurogenomics, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany Nazanin

Mirza-Schreiber * Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA Konstantinos Arfanakis * Department of Diagnostic Radiology and Nuclear Medicine,

Rush University Medical Center, Chicago, IL, USA Konstantinos Arfanakis * Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne, Victoria, Australia David Ames *

National Ageing Research Institute, Royal Melbourne Hospital, Melbourne, Victoria, Australia David Ames * Harvard Medical School, Boston, MA, USA Phil H. Lee, Randy L. Gollub, Robert C Green

 & Jordan W. Smoller * Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Lexington, MA, USA Phil H. Lee * Psychiatric and Neurodevelopmental Genetics Unit,

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA Phil H. Lee & Jordan W. Smoller * Stanley Center for Psychiatric Research, Broad Institute of MIT and

Harvard, Boston, MA, USA Phil H. Lee & Jordan W. Smoller * Amsterdam Public Health Research Institute, VU Medical Center, Amsterdam, the Netherlands Dorret I. Boomsma, Eco J. C. de Geus,

 Jouke-Jan Hottenga, Iryna O. Fedko & Dennis van ‘t Ent * Department of Psychiatry, University of Oxford, Oxford, UK Simon Lovestone * NIHR Dementia Biomedical Research Unit, King’s

College London, London, UK Simon Lovestone * NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway Sudheer Giddaluru, Stephanie Le Hellard, Vidar M. Steen & 

Srdjan Djurovic * Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway Sudheer

Giddaluru, Stephanie Le Hellard & Vidar M. Steen * Centre for integrated Sequencing, Aarhus University, Aarhus, Denmark Manuel Mattheisen * Department of Biomedicine, Aarhus University,

Aarhus, Denmark Manuel Mattheisen * The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Manuel Mattheisen * Department of Clinical Neuroscience,

Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden Manuel Mattheisen, Ingrid Agartz & Erik G. Jönsson * Stockholm Health Care Services, Stockholm County Council,

Stockholm, Sweden Manuel Mattheisen * UCL Queen Square Institute of Neurology, London, UK Dalia Kasperaviciute, Mar Matarin & Sanjay M. Sisodiya * Chalfont Centre for Epilepsy, Bucks, UK

Dalia Kasperaviciute & Sanjay M. Sisodiya * Centre for Youth Mental Health, The University of Melbourne, Melbourne, Victoria, Australia Lianne Schmaal * Orygen, The National Centre of

Excellence in Youth Mental Health, Melbourne, Victoria, Australia Lianne Schmaal * Department of Research and Development, Diakonhjemmet Hospital, Oslo, Norway Ingrid Agartz * Department of

Psychology, University of Bath, Bath, UK Esther Walton * Neuroimaging Unit, Technological Facilities, Valdecilla Biomedical Research Institute IDIVAL, Santander, Spain Diana

Tordesillas-Gutierrez * Avera Institute for Human Genetics, Sioux Falls, SD, USA Gareth E. Davies * Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada Jean Shin, 

Manon Bernard & Zdenka Pausova * Center for Systems Neuroscience, Boston University, Boston, MA, USA Louis N. Vinke * Institute of Clinical Chemistry and Laboratory Medicine, University

Hospital Regensburg, Regensburg, Germany Ralph Burkhardt * Neurodegeneratives Diseases Institute, CNRS UMR 5293, Université de Bordeaux, Bordeaux, France Fabrice Crivello & Bernard

Mazoyer * Pennington Biomedical Research Center, Baton Rouge, LA, USA Owen Carmichael * Department of Adult Psychiatry, Institute for Clinical Medicine, University of Oslo, Oslo, Norway Unn

K. Haukvik * Brain Research Imaging Centre, University of Edinburgh, Edinburgh, UK Benjamin S. Aribisala, Maria C. Valdés Hernández & Mark E. Bastin * Department of Computer Science,

Lagos State University, Ojo, Nigeria Benjamin S. Aribisala * Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia Lachlan T. Strike, Narelle K. Hansell &

 Margaret J. Wright * Ophthalmology and Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore Ching-Yu Cheng * Department of Behavioral Sciences,

Rush University Medical Center, Chicago, IL, USA Debra A. Fleischman * Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, New South Wales,

Australia Amelia A. Assareh, Henry Brodaty, Simone Reppermund, Anbupalam Thalamuthu, Wei Wen, Perminder S. Sachdev & Karen A. Mather * Department of Neurology, Johns Hopkins University

School of Medicine, Baltimore, MD, USA Venkata S. Mattay & Daniel R. Weinberger * Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA Venkata S.

Mattay * Department of Psychology, Center for Brain Science, Harvard University, Cambridge, MA, USA Randy L. Buckner * Section of Gerontology and Geriatrics, Department of Medicine,

University of Perugia, Perugia, Italy Patrizia Mecocci * Center for Multimodal Imaging and Genetics, University of California, San Diego, San Diego, CA, USA Anders M. Dale * Department of

Cognitive Sciences, University of California, San Diego, San Diego, CA, USA Anders M. Dale * Department of Neurosciences, University of California. San Diego, San Diego, CA, USA Anders M.

Dale * Department of Psychiatry, University of California, San Diego, San Diego, CA, USA Anders M. Dale * Department of Radiology, University of California, San Diego, San Diego, CA, USA

Anders M. Dale * Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland Sven Cichon * Institute of Human Genetics, University of Bonn, Bonn, Germany

Sven Cichon & Markus M. Nöthen * Institute for Neuroscience and Medicine: Structural and Functional Organisation of the Brain (INM-1), Research Centre Jülich, Jülich, Germany Sven

Cichon & Thomas W. Mühleisen * Reta Lila Weston Institute, UCL Institute of Neurology, London, UK Mar Matarin * Department of Molecular Neuroscience, UCL Institute of Neurology, London,

UK Mar Matarin * Department of ECE, University of New Mexico, Albuquerque, NM, USA Vince D. Calhoun * The Mind Research Network and LBERI, Albuquerque, NM, USA Vince D. Calhoun & Jessica

A. Turner * Tri-institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State University, Atlanta, GA, USA Vince D. Calhoun & Jessica A. Turner *

Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Québec, Canada M. Mallar Chakravarty * Departments of Psychiatry and Biological and Biomedical Engineering,

McGill University, Montreal, Québec, Canada M. Mallar Chakravarty * Donders Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, the Netherlands Andre F. Marquand, Elena

Shumskaya & Marcel P. Zwiers * Institute for Neuroscience and Medicine: Brain and Behaviour (INM-7), Research Centre Jülich, Jülich, Germany Shahrzad Kharabian Masouleh * Clinical

Neuropsychology Section, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands Jaap Oosterlaan * Emma Neuroscience Group, Department of Pediatrics, Emma Children’s Hospital, Amsterdam

Reproduction & Development, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands Jaap Oosterlaan * LabEx DISTALZ—U1167, RID-AGE-Risk Factors and Molecular Determinants of

Aging-Related Diseases, University of Lille, Lille, France Philippe Amouyel * Inserm U1167, Lille, France Philippe Amouyel * Centre Hospitalier Universitaire Lille, Lille, France Philippe

Amouyel * Institut Pasteur de Lille, Lille, France Philippe Amouyel * Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany Katrin

Hegenscheid & Norbert Hosten * Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Pediatrics at Harbor-UCLA Medical Center,

Torrance, CA, USA Jerome I. Rotter * Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Roskilde, Denmark Andrew J. Schork * Neurogenomics Division, Translational Genomics

Research Institute, Phoenix, AZ, USA Andrew J. Schork & Matthew Huentelman * Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia Greig I. de Zubicaray

 & Katie L. McMahon * Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia Greig I. de Zubicaray & Katie L. McMahon *

Academic Medicine Research Institute, Duke-NUS Medical School, Singapore, Singapore Tien Yin Wong * Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania,

Philadelphia, PA, USA Li Shen * Dementia Centre for Research Collaboration, UNSW, Sydney, New South Wales, Australia Henry Brodaty * 1st Department of Neurology, AHEPA University Hospital,

Aristotle University of Thessaloniki, Thessaloniki, Greece Magda Tsolaki * Division of Mind and Brain Research, D, Corporate member of Freie Universität Berliepartment of Psychiatry and

Psychotherapy, Charité—Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany Susanne Erk, Sebastian Mohnke & Henrik Walter * Brain

Center Rudolf Magnus, Human Neurogenetics Unit, UMC Utrecht, Utrecht, the Netherlands Kristel R. van Eijk * Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in

Ireland, Dublin, Ireland Gianpiero L. Cavalleri * Department of Psychiatry, Leiden University Medical Center, Leiden, the Netherlands Nic J. A. van der Wee * Leiden Institute for Brain and

Cognition, Leiden University Medical Center, Leiden, the Netherlands Nic J. A. van der Wee * Department of Evolution and Genetics, Dagestan State University, Makhachkala, Russia Kazima B.

Bulayeva * University Medical Center Groningen, Department of Psychiatry, University of Groningen, Groningen, the Netherlands Jennifer S. Richards, Daan van Rooij, Catharina A. Hartman &

 Pieter J. Hoekstra * Karakter Child and Adolescent Psychiatry University Center, Nijmegen, the Netherlands Nanda Rommelse & Jan K. Buitelaar * Section Epidemiology of Health Care and

Community Health, Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany Wolfgang Hoffmann * Centre for Clinical Brain Sciences, University of Edinburgh,

Edinburgh, UK Maria C. Valdés Hernández, Mark E. Bastin & Joanna M. Wardlaw * Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of

California, Irvine, Irvine, CA, USA Theo G. M. van Erp * Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, CA, USA Theo G. M. van Erp * Department

of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany Christiane Wolf * Brain and Mind Centre, University of Sydney, Sydney, New South Wales,

Australia John B. J. Kwok * Neuroscience Research Australia, Sydney, New South Wales, Australia John B. J. Kwok, Peter R. Schofield & Karen A. Mather * University of New South Wales,

Sydney, New South Wales, Australia John B. J. Kwok * Department of Internal Medicine, INSERM U 1027, University of Toulouse, Toulouse, France Bruno Vellas * Department of Geriatric Medicine,

INSERM U 1027, University of Toulouse, Toulouse, France Bruno Vellas * Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany Andreas Heinz & 

Nina Romanczuk-Seiferth * Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles, CA, USA Loes M. Olde Loohuis & Roel A. Ophoff * Neurology Division,

Beaumont Hospital, Dublin, Ireland Norman Delanty * Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA Beng-Choon Ho & Thomas H. Wassink *

Interdepartmental Neuroscience Graduate Program, UCLA School of Medicine, Los Angeles, CA, USA Christopher R. K. Ching * Imaging of Dementia and Aging Laboratory, Department of Neurology,

University of California, Davis, Davis, CA, USA Baljeet Singh, Pauline Maillard & Evan Fletcher * Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

Albert Hofman * School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands Dennis van der Meer * Interfaculty

Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany Georg Homuth * Kaiser Permanent Washington Health Research Institute, Seattle, WA, USA

Bruce M. Psaty * Department of Epidemiology, University of Washington, Seattle, WA, USA Bruce M. Psaty & William T. Longstreth Jr * Department of Health Services, University of

Washington, Seattle, WA, USA Bruce M. Psaty * Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia Grant W. Montgomery * Medical and Molecular

Genetics, Indiana University School of Medicine, Indianapolis, IN, USA Tatiana M. Foroud & Andrew J. Saykin * Department of Developmental Disability Neuropsychiatry, School of

Psychiatry, UNSW Medicine, Sydney, New South Wales, Australia Simone Reppermund * Biomedical Research Unit for Dementia, King’s College London, London, UK Andrew Simmons * Department of

Neuroimaging, Institute of Psychiatry, King’s College London, London, UK Andrew Simmons * Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska

Institute, Stockholm, Sweden Andrew Simmons * Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA Robert C Green * Section of Computational

Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA Honghuang Lin * Department of Radiology, Mayo Clinic, Rochester, MN, USA Clifford R. Jack Jr *

School of Medical Sciences, UNSW, Sydney, New South Wales, Australia Peter R. Schofield * Department of Biomedicine, University of Basel, Basel, Switzerland Thomas W. Mühleisen * Cécile and

Oskar Vogt Institute for Brain Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany Thomas W. Mühleisen * Department of Psychiatry and Human Behavior, University of

California, Irvine, Irvine, CA, USA Steven G. Potkin * Laboratory of Neuro Imaging, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the

University of Southern California, Los Angeles, CA, USA Arthur W. Toga * Radiation Sciences, Umeå University, Umeå, Sweden Lars Nyberg * Department of Radiology, Massachusetts General

Hospital, Harvard Medical School, Boston, MA, USA Douglas N. Greve * Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands André G. Uitterlinden * Department of

Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA Daniel R. Weinberger * Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore,

MD, USA Daniel R. Weinberger * Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA Daniel R. Weinberger * Imaging Physics, Faculty of Applied Sciences,

Delft University of Technology, Delft, the Netherlands Wiro J. Niessen * Institut Pasteur, Paris, France Roberto Toro * Department of Neurology, CHU de Bordeaux, Bordeaux, France Christophe

Tzourio & Stéphanie Debette * Department of Neurology, University of Washington, Seattle, WA, USA William T. Longstreth Jr * Department of Neurology, Erasmus MC, Rotterdam, the

Netherlands M. Kamran Ikram * Cognitive Neuroscience Center, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Marie-Jose van Tol * Bloorview Research

Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada Tomas Paus * Department of Psychology, University of Toronto, Toronto, Ontario, Canada Tomas Paus *

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Tomas Paus * Clinic for Cognitive Neurology, University Clinic Leipzig, Leipzig, Germany Matthias L. Schroeter *

HMNC Brain Health, Munich, Germany Florian Holsboer * Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium Chantal Depondt & Massimo Pandolfo *

Department of Psychology, Georgia State University, Atlanta, GA, USA Jessica A. Turner * Department of Medical Genetics, Oslo University Hospital, Oslo, Norway Srdjan Djurovic * Munich

Cluster for Systems Neurology (SyNergy), Munich, Germany Bertram Müller-Myhsok * Institute of Translational Medicine, University of Liverpool, Liverpool, UK Bertram Müller-Myhsok * Institute

of Clinical Medicine—Neurology, University of Eastern Finland, Kuopio, Finland Hilkka Soininen * Neurocentre Neurology, Kuopio University Hospital, Kuopio, Finland Hilkka Soininen *

Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany Matthias Nauck * German Center for Cardiovascular Research (partner site

Greifswald), Greifswald, Germany Matthias Nauck & Henry Völzke * Department of Neuroinformatics, Araya, Tokyo, Japan Ryota Kanai * Institute of Cognitive Neuroscience, University College

London, London, UK Ryota Kanai * School of Psychology, University of Sussex, Brighton, UK Ryota Kanai * Department of Neurobiology, Care Sciences and Society, Karolinska Institutet,

Stockholm, Sweden Eric Westman * Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA René S. Kahn * Department of Child and Adolescent Psychiatry/Psychology,

Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands Tonya White & Neeltje E. M. van Haren * Department of Clinical Genetics, Maastricht University Medical Center,

Maastricht, the Netherlands Han G. Brunner * GROW School for Oncology and Developmental Biology, Maastricht, the Netherlands Han G. Brunner * Centre for Advanced Imaging, University of

Queensland, Brisbane, Queensland, Australia Margaret J. Wright * Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany Markus M. Nöthen * Department of Psychiatry,

Erasmus Medical Center, Rotterdam, the Netherlands Roel A. Ophoff * Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, New South Wales, Australia Perminder S. Sachdev *

Department of Psychology, VU University Amsterdam, Amsterdam, the Netherlands Dirk J. Heslenfeld * Center for Imaging of Neurodegenerative Disease, San Francisco VA Medical Center,

University of California, San Francisco, San Francisco, CA, USA Michael W. Weiner * Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco,

CA, USA Michael W. Weiner * Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands Cornelia M. van Duijn * Human Genetics Center, University of Texas Health

Science Center at Houston, Houston, TX, USA Myriam Fornage * UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK Joanna M. Wardlaw * Department of Neurology, Center for

Neuroscience, University of California, Davis, Sacramento, CA, USA Charles DeCarli * Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA Joshua M. Shulman * Department

of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA Joshua M. Shulman * Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX,

USA Joshua M. Shulman Authors * Claudia L. Satizabal View author publications You can also search for this author inPubMed Google Scholar * Hieab H. H. Adams View author publications You can

also search for this author inPubMed Google Scholar * Derrek P. Hibar View author publications You can also search for this author inPubMed Google Scholar * Charles C. White View author

publications You can also search for this author inPubMed Google Scholar * Maria J. Knol View author publications You can also search for this author inPubMed Google Scholar * Jason L. Stein

View author publications You can also search for this author inPubMed Google Scholar * Markus Scholz View author publications You can also search for this author inPubMed Google Scholar *

Muralidharan Sargurupremraj View author publications You can also search for this author inPubMed Google Scholar * Neda Jahanshad View author publications You can also search for this author

inPubMed Google Scholar * Gennady V. Roshchupkin View author publications You can also search for this author inPubMed Google Scholar * Albert V. Smith View author publications You can also

search for this author inPubMed Google Scholar * Joshua C. Bis View author publications You can also search for this author inPubMed Google Scholar * Xueqiu Jian View author publications

You can also search for this author inPubMed Google Scholar * Michelle Luciano View author publications You can also search for this author inPubMed Google Scholar * Edith Hofer View author

publications You can also search for this author inPubMed Google Scholar * Alexander Teumer View author publications You can also search for this author inPubMed Google Scholar * Sven J. van

der Lee View author publications You can also search for this author inPubMed Google Scholar * Jingyun Yang View author publications You can also search for this author inPubMed Google

Scholar * Lisa R. Yanek View author publications You can also search for this author inPubMed Google Scholar * Tom V. Lee View author publications You can also search for this author

inPubMed Google Scholar * Shuo Li View author publications You can also search for this author inPubMed Google Scholar * Yanhui Hu View author publications You can also search for this

author inPubMed Google Scholar * Jia Yu Koh View author publications You can also search for this author inPubMed Google Scholar * John D. Eicher View author publications You can also search

for this author inPubMed Google Scholar * Sylvane Desrivières View author publications You can also search for this author inPubMed Google Scholar * Alejandro Arias-Vasquez View author

publications You can also search for this author inPubMed Google Scholar * Ganesh Chauhan View author publications You can also search for this author inPubMed Google Scholar * Lavinia

Athanasiu View author publications You can also search for this author inPubMed Google Scholar * Miguel E. Rentería View author publications You can also search for this author inPubMed 

Google Scholar * Sungeun Kim View author publications You can also search for this author inPubMed Google Scholar * David Hoehn View author publications You can also search for this author

inPubMed Google Scholar * Nicola J. Armstrong View author publications You can also search for this author inPubMed Google Scholar * Qiang Chen View author publications You can also search

for this author inPubMed Google Scholar * Avram J. Holmes View author publications You can also search for this author inPubMed Google Scholar * Anouk den Braber View author publications You

can also search for this author inPubMed Google Scholar * Iwona Kloszewska View author publications You can also search for this author inPubMed Google Scholar * Micael Andersson View

author publications You can also search for this author inPubMed Google Scholar * Thomas Espeseth View author publications You can also search for this author inPubMed Google Scholar *

Oliver Grimm View author publications You can also search for this author inPubMed Google Scholar * Lucija Abramovic View author publications You can also search for this author inPubMed 

Google Scholar * Saud Alhusaini View author publications You can also search for this author inPubMed Google Scholar * Yuri Milaneschi View author publications You can also search for this

author inPubMed Google Scholar * Martina Papmeyer View author publications You can also search for this author inPubMed Google Scholar * Tomas Axelsson View author publications You can also

search for this author inPubMed Google Scholar * Stefan Ehrlich View author publications You can also search for this author inPubMed Google Scholar * Roberto Roiz-Santiañez View author

publications You can also search for this author inPubMed Google Scholar * Bernd Kraemer View author publications You can also search for this author inPubMed Google Scholar * Asta K. Håberg

View author publications You can also search for this author inPubMed Google Scholar * Hannah J. Jones View author publications You can also search for this author inPubMed Google Scholar *

G. Bruce Pike View author publications You can also search for this author inPubMed Google Scholar * Dan J. Stein View author publications You can also search for this author inPubMed 

Google Scholar * Allison Stevens View author publications You can also search for this author inPubMed Google Scholar * Janita Bralten View author publications You can also search for this

author inPubMed Google Scholar * Meike W. Vernooij View author publications You can also search for this author inPubMed Google Scholar * Tamara B. Harris View author publications You can

also search for this author inPubMed Google Scholar * Irina Filippi View author publications You can also search for this author inPubMed Google Scholar * A. Veronica Witte View author

publications You can also search for this author inPubMed Google Scholar * Tulio Guadalupe View author publications You can also search for this author inPubMed Google Scholar * Katharina

Wittfeld View author publications You can also search for this author inPubMed Google Scholar * Thomas H. Mosley View author publications You can also search for this author inPubMed Google

Scholar * James T. Becker View author publications You can also search for this author inPubMed Google Scholar * Nhat Trung Doan View author publications You can also search for this author

inPubMed Google Scholar * Saskia P. Hagenaars View author publications You can also search for this author inPubMed Google Scholar * Yasaman Saba View author publications You can also search

for this author inPubMed Google Scholar * Gabriel Cuellar-Partida View author publications You can also search for this author inPubMed Google Scholar * Najaf Amin View author publications

You can also search for this author inPubMed Google Scholar * Saima Hilal View author publications You can also search for this author inPubMed Google Scholar * Kwangsik Nho View author

publications You can also search for this author inPubMed Google Scholar * Nazanin Mirza-Schreiber View author publications You can also search for this author inPubMed Google Scholar *

Konstantinos Arfanakis View author publications You can also search for this author inPubMed Google Scholar * Diane M. Becker View author publications You can also search for this author

inPubMed Google Scholar * David Ames View author publications You can also search for this author inPubMed Google Scholar * Aaron L. Goldman View author publications You can also search for

this author inPubMed Google Scholar * Phil H. Lee View author publications You can also search for this author inPubMed Google Scholar * Dorret I. Boomsma View author publications You can

also search for this author inPubMed Google Scholar * Simon Lovestone View author publications You can also search for this author inPubMed Google Scholar * Sudheer Giddaluru View author

publications You can also search for this author inPubMed Google Scholar * Stephanie Le Hellard View author publications You can also search for this author inPubMed Google Scholar * Manuel

Mattheisen View author publications You can also search for this author inPubMed Google Scholar * Marc M. Bohlken View author publications You can also search for this author inPubMed Google

Scholar * Dalia Kasperaviciute View author publications You can also search for this author inPubMed Google Scholar * Lianne Schmaal View author publications You can also search for this

author inPubMed Google Scholar * Stephen M. Lawrie View author publications You can also search for this author inPubMed Google Scholar * Ingrid Agartz View author publications You can also

search for this author inPubMed Google Scholar * Esther Walton View author publications You can also search for this author inPubMed Google Scholar * Diana Tordesillas-Gutierrez View author

publications You can also search for this author inPubMed Google Scholar * Gareth E. Davies View author publications You can also search for this author inPubMed Google Scholar * Jean Shin

View author publications You can also search for this author inPubMed Google Scholar * Jonathan C. Ipser View author publications You can also search for this author inPubMed Google Scholar

* Louis N. Vinke View author publications You can also search for this author inPubMed Google Scholar * Martine Hoogman View author publications You can also search for this author inPubMed 

Google Scholar * Tianye Jia View author publications You can also search for this author inPubMed Google Scholar * Ralph Burkhardt View author publications You can also search for this

author inPubMed Google Scholar * Marieke Klein View author publications You can also search for this author inPubMed Google Scholar * Fabrice Crivello View author publications You can also

search for this author inPubMed Google Scholar * Deborah Janowitz View author publications You can also search for this author inPubMed Google Scholar * Owen Carmichael View author

publications You can also search for this author inPubMed Google Scholar * Unn K. Haukvik View author publications You can also search for this author inPubMed Google Scholar * Benjamin S.

Aribisala View author publications You can also search for this author inPubMed Google Scholar * Helena Schmidt View author publications You can also search for this author inPubMed Google

Scholar * Lachlan T. Strike View author publications You can also search for this author inPubMed Google Scholar * Ching-Yu Cheng View author publications You can also search for this author

inPubMed Google Scholar * Shannon L. Risacher View author publications You can also search for this author inPubMed Google Scholar * Benno Pütz View author publications You can also search

for this author inPubMed Google Scholar * Debra A. Fleischman View author publications You can also search for this author inPubMed Google Scholar * Amelia A. Assareh View author

publications You can also search for this author inPubMed Google Scholar * Venkata S. Mattay View author publications You can also search for this author inPubMed Google Scholar * Randy L.

Buckner View author publications You can also search for this author inPubMed Google Scholar * Patrizia Mecocci View author publications You can also search for this author inPubMed Google

Scholar * Anders M. Dale View author publications You can also search for this author inPubMed Google Scholar * Sven Cichon View author publications You can also search for this author

inPubMed Google Scholar * Marco P. Boks View author publications You can also search for this author inPubMed Google Scholar * Mar Matarin View author publications You can also search for

this author inPubMed Google Scholar * Brenda W. J. H. Penninx View author publications You can also search for this author inPubMed Google Scholar * Vince D. Calhoun View author publications

You can also search for this author inPubMed Google Scholar * M. Mallar Chakravarty View author publications You can also search for this author inPubMed Google Scholar * Andre F. Marquand

View author publications You can also search for this author inPubMed Google Scholar * Christine Macare View author publications You can also search for this author inPubMed Google Scholar *

Shahrzad Kharabian Masouleh View author publications You can also search for this author inPubMed Google Scholar * Jaap Oosterlaan View author publications You can also search for this

author inPubMed Google Scholar * Philippe Amouyel View author publications You can also search for this author inPubMed Google Scholar * Katrin Hegenscheid View author publications You can

also search for this author inPubMed Google Scholar * Jerome I. Rotter View author publications You can also search for this author inPubMed Google Scholar * Andrew J. Schork View author

publications You can also search for this author inPubMed Google Scholar * David C. M. Liewald View author publications You can also search for this author inPubMed Google Scholar * Greig I.

de Zubicaray View author publications You can also search for this author inPubMed Google Scholar * Tien Yin Wong View author publications You can also search for this author inPubMed 

Google Scholar * Li Shen View author publications You can also search for this author inPubMed Google Scholar * Philipp G. Sämann View author publications You can also search for this author

inPubMed Google Scholar * Henry Brodaty View author publications You can also search for this author inPubMed Google Scholar * Joshua L. Roffman View author publications You can also search

for this author inPubMed Google Scholar * Eco J. C. de Geus View author publications You can also search for this author inPubMed Google Scholar * Magda Tsolaki View author publications You

can also search for this author inPubMed Google Scholar * Susanne Erk View author publications You can also search for this author inPubMed Google Scholar * Kristel R. van Eijk View author

publications You can also search for this author inPubMed Google Scholar * Gianpiero L. Cavalleri View author publications You can also search for this author inPubMed Google Scholar * Nic

J. A. van der Wee View author publications You can also search for this author inPubMed Google Scholar * Andrew M. McIntosh View author publications You can also search for this author

inPubMed Google Scholar * Randy L. Gollub View author publications You can also search for this author inPubMed Google Scholar * Kazima B. Bulayeva View author publications You can also

search for this author inPubMed Google Scholar * Manon Bernard View author publications You can also search for this author inPubMed Google Scholar * Jennifer S. Richards View author

publications You can also search for this author inPubMed Google Scholar * Jayandra J. Himali View author publications You can also search for this author inPubMed Google Scholar * Markus

Loeffler View author publications You can also search for this author inPubMed Google Scholar * Nanda Rommelse View author publications You can also search for this author inPubMed Google

Scholar * Wolfgang Hoffmann View author publications You can also search for this author inPubMed Google Scholar * Lars T. Westlye View author publications You can also search for this

author inPubMed Google Scholar * Maria C. Valdés Hernández View author publications You can also search for this author inPubMed Google Scholar * Narelle K. Hansell View author publications

You can also search for this author inPubMed Google Scholar * Theo G. M. van Erp View author publications You can also search for this author inPubMed Google Scholar * Christiane Wolf View

author publications You can also search for this author inPubMed Google Scholar * John B. J. Kwok View author publications You can also search for this author inPubMed Google Scholar * Bruno

Vellas View author publications You can also search for this author inPubMed Google Scholar * Andreas Heinz View author publications You can also search for this author inPubMed Google

Scholar * Loes M. Olde Loohuis View author publications You can also search for this author inPubMed Google Scholar * Norman Delanty View author publications You can also search for this

author inPubMed Google Scholar * Beng-Choon Ho View author publications You can also search for this author inPubMed Google Scholar * Christopher R. K. Ching View author publications You can

also search for this author inPubMed Google Scholar * Elena Shumskaya View author publications You can also search for this author inPubMed Google Scholar * Baljeet Singh View author

publications You can also search for this author inPubMed Google Scholar * Albert Hofman View author publications You can also search for this author inPubMed Google Scholar * Dennis van der

Meer View author publications You can also search for this author inPubMed Google Scholar * Georg Homuth View author publications You can also search for this author inPubMed Google Scholar

* Bruce M. Psaty View author publications You can also search for this author inPubMed Google Scholar * Mark E. Bastin View author publications You can also search for this author inPubMed 

Google Scholar * Grant W. Montgomery View author publications You can also search for this author inPubMed Google Scholar * Tatiana M. Foroud View author publications You can also search for

this author inPubMed Google Scholar * Simone Reppermund View author publications You can also search for this author inPubMed Google Scholar * Jouke-Jan Hottenga View author publications

You can also search for this author inPubMed Google Scholar * Andrew Simmons View author publications You can also search for this author inPubMed Google Scholar * Andreas Meyer-Lindenberg

View author publications You can also search for this author inPubMed Google Scholar * Wiepke Cahn View author publications You can also search for this author inPubMed Google Scholar *

Christopher D. Whelan View author publications You can also search for this author inPubMed Google Scholar * Marjolein M. J. van Donkelaar View author publications You can also search for

this author inPubMed Google Scholar * Qiong Yang View author publications You can also search for this author inPubMed Google Scholar * Norbert Hosten View author publications You can also

search for this author inPubMed Google Scholar * Robert C Green View author publications You can also search for this author inPubMed Google Scholar * Anbupalam Thalamuthu View author

publications You can also search for this author inPubMed Google Scholar * Sebastian Mohnke View author publications You can also search for this author inPubMed Google Scholar * Hilleke E.

Hulshoff Pol View author publications You can also search for this author inPubMed Google Scholar * Honghuang Lin View author publications You can also search for this author inPubMed Google

Scholar * Clifford R. Jack Jr View author publications You can also search for this author inPubMed Google Scholar * Peter R. Schofield View author publications You can also search for this

author inPubMed Google Scholar * Thomas W. Mühleisen View author publications You can also search for this author inPubMed Google Scholar * Pauline Maillard View author publications You can

also search for this author inPubMed Google Scholar * Steven G. Potkin View author publications You can also search for this author inPubMed Google Scholar * Wei Wen View author

publications You can also search for this author inPubMed Google Scholar * Evan Fletcher View author publications You can also search for this author inPubMed Google Scholar * Arthur W. Toga

View author publications You can also search for this author inPubMed Google Scholar * Oliver Gruber View author publications You can also search for this author inPubMed Google Scholar *

Matthew Huentelman View author publications You can also search for this author inPubMed Google Scholar * George Davey Smith View author publications You can also search for this author

inPubMed Google Scholar * Lenore J. Launer View author publications You can also search for this author inPubMed Google Scholar * Lars Nyberg View author publications You can also search for

this author inPubMed Google Scholar * Erik G. Jönsson View author publications You can also search for this author inPubMed Google Scholar * Benedicto Crespo-Facorro View author

publications You can also search for this author inPubMed Google Scholar * Nastassja Koen View author publications You can also search for this author inPubMed Google Scholar * Douglas N.

Greve View author publications You can also search for this author inPubMed Google Scholar * André G. Uitterlinden View author publications You can also search for this author inPubMed 

Google Scholar * Daniel R. Weinberger View author publications You can also search for this author inPubMed Google Scholar * Vidar M. Steen View author publications You can also search for

this author inPubMed Google Scholar * Iryna O. Fedko View author publications You can also search for this author inPubMed Google Scholar * Nynke A. Groenewold View author publications You

can also search for this author inPubMed Google Scholar * Wiro J. Niessen View author publications You can also search for this author inPubMed Google Scholar * Roberto Toro View author

publications You can also search for this author inPubMed Google Scholar * Christophe Tzourio View author publications You can also search for this author inPubMed Google Scholar * William

T. Longstreth Jr View author publications You can also search for this author inPubMed Google Scholar * M. Kamran Ikram View author publications You can also search for this author inPubMed 

Google Scholar * Jordan W. Smoller View author publications You can also search for this author inPubMed Google Scholar * Marie-Jose van Tol View author publications You can also search for

this author inPubMed Google Scholar * Jessika E. Sussmann View author publications You can also search for this author inPubMed Google Scholar * Tomas Paus View author publications You can

also search for this author inPubMed Google Scholar * Hervé Lemaître View author publications You can also search for this author inPubMed Google Scholar * Matthias L. Schroeter View author

publications You can also search for this author inPubMed Google Scholar * Bernard Mazoyer View author publications You can also search for this author inPubMed Google Scholar * Ole A.

Andreassen View author publications You can also search for this author inPubMed Google Scholar * Florian Holsboer View author publications You can also search for this author inPubMed 

Google Scholar * Chantal Depondt View author publications You can also search for this author inPubMed Google Scholar * Dick J. Veltman View author publications You can also search for this

author inPubMed Google Scholar * Jessica A. Turner View author publications You can also search for this author inPubMed Google Scholar * Zdenka Pausova View author publications You can also

search for this author inPubMed Google Scholar * Gunter Schumann View author publications You can also search for this author inPubMed Google Scholar * Daan van Rooij View author

publications You can also search for this author inPubMed Google Scholar * Srdjan Djurovic View author publications You can also search for this author inPubMed Google Scholar * Ian J. Deary

View author publications You can also search for this author inPubMed Google Scholar * Katie L. McMahon View author publications You can also search for this author inPubMed Google Scholar

* Bertram Müller-Myhsok View author publications You can also search for this author inPubMed Google Scholar * Rachel M. Brouwer View author publications You can also search for this author

inPubMed Google Scholar * Hilkka Soininen View author publications You can also search for this author inPubMed Google Scholar * Massimo Pandolfo View author publications You can also search

for this author inPubMed Google Scholar * Thomas H. Wassink View author publications You can also search for this author inPubMed Google Scholar * Joshua W. Cheung View author publications

You can also search for this author inPubMed Google Scholar * Thomas Wolfers View author publications You can also search for this author inPubMed Google Scholar * Jean-Luc Martinot View

author publications You can also search for this author inPubMed Google Scholar * Marcel P. Zwiers View author publications You can also search for this author inPubMed Google Scholar *

Matthias Nauck View author publications You can also search for this author inPubMed Google Scholar * Ingrid Melle View author publications You can also search for this author inPubMed 

Google Scholar * Nicholas G. Martin View author publications You can also search for this author inPubMed Google Scholar * Ryota Kanai View author publications You can also search for this

author inPubMed Google Scholar * Eric Westman View author publications You can also search for this author inPubMed Google Scholar * René S. Kahn View author publications You can also search

for this author inPubMed Google Scholar * Sanjay M. Sisodiya View author publications You can also search for this author inPubMed Google Scholar * Tonya White View author publications You

can also search for this author inPubMed Google Scholar * Arvin Saremi View author publications You can also search for this author inPubMed Google Scholar * Hans van Bokhoven View author

publications You can also search for this author inPubMed Google Scholar * Han G. Brunner View author publications You can also search for this author inPubMed Google Scholar * Henry Völzke

View author publications You can also search for this author inPubMed Google Scholar * Margaret J. Wright View author publications You can also search for this author inPubMed Google Scholar

* Dennis van ‘t Ent View author publications You can also search for this author inPubMed Google Scholar * Markus M. Nöthen View author publications You can also search for this author

inPubMed Google Scholar * Roel A. Ophoff View author publications You can also search for this author inPubMed Google Scholar * Jan K. Buitelaar View author publications You can also search

for this author inPubMed Google Scholar * Guillén Fernández View author publications You can also search for this author inPubMed Google Scholar * Perminder S. Sachdev View author

publications You can also search for this author inPubMed Google Scholar * Marcella Rietschel View author publications You can also search for this author inPubMed Google Scholar * Neeltje

E. M. van Haren View author publications You can also search for this author inPubMed Google Scholar * Simon E. Fisher View author publications You can also search for this author inPubMed 

Google Scholar * Alexa S. Beiser View author publications You can also search for this author inPubMed Google Scholar * Clyde Francks View author publications You can also search for this

author inPubMed Google Scholar * Andrew J. Saykin View author publications You can also search for this author inPubMed Google Scholar * Karen A. Mather View author publications You can also

search for this author inPubMed Google Scholar * Nina Romanczuk-Seiferth View author publications You can also search for this author inPubMed Google Scholar * Catharina A. Hartman View

author publications You can also search for this author inPubMed Google Scholar * Anita L. DeStefano View author publications You can also search for this author inPubMed Google Scholar *

Dirk J. Heslenfeld View author publications You can also search for this author inPubMed Google Scholar * Michael W. Weiner View author publications You can also search for this author

inPubMed Google Scholar * Henrik Walter View author publications You can also search for this author inPubMed Google Scholar * Pieter J. Hoekstra View author publications You can also search

for this author inPubMed Google Scholar * Paul A. Nyquist View author publications You can also search for this author inPubMed Google Scholar * Barbara Franke View author publications You

can also search for this author inPubMed Google Scholar * David A. Bennett View author publications You can also search for this author inPubMed Google Scholar * Hans J. Grabe View author

publications You can also search for this author inPubMed Google Scholar * Andrew D. Johnson View author publications You can also search for this author inPubMed Google Scholar *

Christopher Chen View author publications You can also search for this author inPubMed Google Scholar * Cornelia M. van Duijn View author publications You can also search for this author

inPubMed Google Scholar * Oscar L. Lopez View author publications You can also search for this author inPubMed Google Scholar * Myriam Fornage View author publications You can also search

for this author inPubMed Google Scholar * Joanna M. Wardlaw View author publications You can also search for this author inPubMed Google Scholar * Reinhold Schmidt View author publications

You can also search for this author inPubMed Google Scholar * Charles DeCarli View author publications You can also search for this author inPubMed Google Scholar * Philip L. De Jager View

author publications You can also search for this author inPubMed Google Scholar * Arno Villringer View author publications You can also search for this author inPubMed Google Scholar *

Stéphanie Debette View author publications You can also search for this author inPubMed Google Scholar * Vilmundur Gudnason View author publications You can also search for this author

inPubMed Google Scholar * Sarah E. Medland View author publications You can also search for this author inPubMed Google Scholar * Joshua M. Shulman View author publications You can also

search for this author inPubMed Google Scholar * Paul M. Thompson View author publications You can also search for this author inPubMed Google Scholar * Sudha Seshadri View author

publications You can also search for this author inPubMed Google Scholar * M. Arfan Ikram View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS

C.L.S. drafted the manuscript with contributions from H.H.H.A., D.P.H., C.C.W., T.V.L., A.A.-V., S.Ehrlich., A.K.H., M.W.V., D.J., T.G.M.v.E., C.D.W., M.J.W., S.E.F., K.A.M., P.J.H., B.F.,

H.J.G., A.D.J., O.L.L., S.Debette, S.E.M., J.M.S., P.M.T., S.S. and M.A.I. M.S., N.J., L.R.Y., T.V.L., G.C., L.A., M.E.R., A.d.B., I.K., M.A., S.A., S.E., R.R.-S., A.K.H., H.J.J.,

A.Stevens., J.B., M.W.V., A.V.W., K.W., N.A., S.H., A.L.G., P.H.L., S.G., S.L.H., D.K., L.Schmaal, S.M.L., I.A., E.W., D.T.-G., J.C.I., L.N.V., R.B., F.C., D.J., O.C., U.K.H., B.S.A.,

C.-Y.C., A.A.A., M.P.B., A.F.M., S.K.M., P.A., A.J.Schork., D.C.M.L., T.Y.W., L.Shen, P.G.S., E.J.C.d.G., M.T., K.R.v.E., N.J.A.v.d.W., A.M.M., J.S.R., N.R., W.H., M.C.V.H., J.B.J.K.,

L.M.O.L., A.Hofman, G.H., M.E.B., S.R., J.-J.H., A.Simmons, N.H., P.R.S., T.W.M., P.Maillard, O.Gruber, N.A.G., J.E.S., H.Lemaître, B.M.-M., D.v.R., I.J.D., R.M.B., I.M., R.K., H.v.B.,

M.J.W., D.v.‘t.E., M.M.N., S.E.F., A.S.B., K.A.M., N.R.-S., D.J.H., H.J.G., C.M.v.D., J.M.W., C.DeCarli, P.L.D.J. and V.G. contributed to the preparation of data. C.L.S., H.H.H.A., D.P.H.,

M.J.K., J.L.S., M.S., M.Sargurupremraj, N.J., G.V.R., A.V.S., J.C.B., X.J., M.Luciano., E.H., A.Teumer, S.J.v.d.L., J.Y., L.R.Y., S.L., K.J.Y., G.C., M.E.R., N.J.A., H.J.J., A.V.W., S.H.,

N.M.S., S.G., D.T.G., J.S., C.-Y.C., L.M.O.L., Q.Y., A.Thalamuthu, I.O.F., D.v.‘t.E., C.Depondt and P.L.D.J. performed the statistical analyses. C.L.S., H.H.H.A., C.C.W., M.J.K., T.V.L.,

S.L., Y.H., K.J.Y., J.D.E., Q.Y. and A.D.J. carried out the downstream analyses. All authors reviewed the manuscript for intellectual content. CORRESPONDING AUTHORS Correspondence to Claudia

L. Satizabal or M. Arfan Ikram. ETHICS DECLARATIONS COMPETING INTERESTS D.P.H. is currently an employee at Genentech. D.J. has received travel and speaker’s honoraria from Janssen–Cilag, as

well as research funding from DFG. R.L.B. is a consultant for Pfizer and Roche. P.A. is a scientific adviser for Genoscreen. T.Y.W. is a consultant and advisory board member for Allergan,

Bayer, Boehringer–Ingelheim, Genentech, Merck, Novartis, Oxurion (formerly ThromboGenics) and Roche, and is a co-founder of Plano and EyRiS. A.M.M. has received grant support from Eli Lilly,

Janssen, Pfizer and the Sackler Trust. B.M.P. serves on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. A.M.-L. is a member of the advisory

board for the Lundbeck International Neuroscience Foundation and Brainsway, a member of the editorial board for the American Association for the Advancement of Science and Elsevier, a

faculty member of the Lundbeck International Neuroscience Foundation and a consultant for Boehringer Ingelheim. W.J.N. is the founder and scientific lead of Quantib BV, in addition to being

a shareholder. M.M.N. is a shareholder of Life & Brain, receives a salary from Life & Brain, has received support from Shire for attending conferences and has received financial

remuneration from the Lundbeck Foundation, Robert Bosch Foundation and Deutsches Ärzteblatt for participation in scientific advisory boards. B.F. has received educational speaking fees from

Shire and Medice. H.J.G. has received travel grants and speaker’s honoraria from Fresenius Medical Care, Neuraxpharm and Janssen–Cilag, as well as research funding from Fresenius Medical

Care. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION Supplementary Note and Figs. 1–4 REPORTING SUMMARY SUPPLEMENTARY TABLES Supplementary Tables 1–21 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS

ARTICLE CITE THIS ARTICLE Satizabal, C.L., Adams, H.H.H., Hibar, D.P. _et al._ Genetic architecture of subcortical brain structures in 38,851 individuals. _Nat Genet_ 51, 1624–1636 (2019).

https://doi.org/10.1038/s41588-019-0511-y Download citation * Received: 26 September 2017 * Accepted: 05 September 2019 * Published: 21 October 2019 * Issue Date: November 2019 * DOI:

https://doi.org/10.1038/s41588-019-0511-y SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative