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Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept
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Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.
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Self-citation
Metadata
- Authors
- Schizophrenia Working Group of the Psychiatric Genomics Consortium, Franke, B., Enigma Consortium, Stein, J. L., Ripke, S., Anttila, V., Hibar, D. P., van Hulzen, K. J. E., Arias-Vasquez, A., Smoller, J. W., Nichols, T. E., Neale, M. C., McIntosh, A. M., Lee, P., McMahon, F. J., Meyer-Lindenberg, A., Mattheisen, M., Andreassen, O. A., Gruber, O., Sachdev, P. S., Roiz-Santiañez, R., Saykin, A. J., Ehrlich, S., Mather, K. A., Turner, J. A., Schwarz, E., Thalamuthu, A., Yao, Y., Ho, Y. Y. W., Martin, N. G., Wright, M. J., O'Donovan, M. C., Thompson, P. M., Neale, B. M., Medland, S. E., & Sullivan, P. F.
- Affiliations
- Radboud University Nijmegen (NL)
- University of Southern California (US)
- Broad Institute (US)
- University of Warwick (GB)
- Virginia Commonwealth University (US)
- Royal Edinburgh Hospital (GB)
- Aarhus University (DK)
- Oslo University Hospital (NO)
- Universitätsmedizin Göttingen (DE)
- UNSW Sydney (AU)
- Indiana University Indianapolis (US)
- Technische Universität Dresden (DE)
- Mind Research Network (US)
- Heidelberg University (DE)
- National Institutes of Health (US)
- QIMR Berghofer Medical Research Institute (AU)
- The University of Queensland (AU)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Franke, Barbara
- Sullivan, Patrick F
- ORCID
- Franke, Barbara
- Stein, Jason L
- Ripke, Stephan
- Anttila, Verneri
- Smoller, Jordan W
- Nichols, Thomas E
- Neale, Michael C
- McIntosh, Andrew M
- Lee, Phil
- Mattheisen, Manuel
- Andreassen, Ole A
- Gruber, Oliver
- Sachdev, Perminder S
- Saykin, Andrew J
- Ehrlich, Stefan
- Mather, Karen A
- Turner, Jessica A
- Schwarz, Emanuel
- Thalamuthu, Anbupalam
- Martin, Nicholas G
- Wright, Margaret J
- Thompson, Paul M
- Neale, Benjamin M
- Medland, Sarah E
- Sullivan, Patrick F
- Venue
- Nature Neuroscience
- Published
- 2016-02-01
- Volume
- 19
- Issue
- 3
- Pages
- 420-431
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4852730
- OpenAlex
- W2272246971
- Cited by
- 216
- References
- 39
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 10 · 2023: 9 · 2022: 18 · 2021: 16 · 2020: 22 · 2019: 35 · 2018: 39 · 2017: 41 · 2016: 14
- FWCI
- 37.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Bristol Research (University of Bristol) (publishedVersion)
- UWA Profiles and Research Repository (UWA) (acceptedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Lancaster EPrints (Lancaster University) (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- UEF eRepo (University of Eastern Finland) (submittedVersion, other-oa)
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- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- ScholarWorks @ UTRGV (The University of Texas Rio Grande Valley) (submittedVersion)
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- Purdue University Indianapolis (Indiana University) (submittedVersion)
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- Funders
- National Science Foundation (R01 MH100141, U01 MH081928, P41 EB015922, R01 EB008432, 1229450, 12,13, FP7/2007-2013, W81XWH-12-2-0012, U01 AG024904)
- U.S. Department of Defense (U01 AG024904, W81XWH, W81XWH-12-2-, W81XWH1220012, AG024904)
- Foundation for the National Institutes of Health (1RC2 MH089995, R01 HD050735, W81XWH-12-2-0012, P41 EB015922, MH085542, MH100141, U54EB020403, EB020403, U01AG024904, NWO/SPI 56-464-14192, MH085548, R01MH62873, AG024904, EB015922)
- Autism Speaks (115300)
- U.S. Department of Veterans Affairs (29,30, 10-000-1002, U01 AG024904)
- Alzheimer's Association (115300, U01 AG024904, W81XWH-12-2-0012)
- Bristol-Myers Squibb (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Eli Lilly and Company (090532/Z/09/Z, U01 AG024904, AG024904, W81XWH-12-2-0012)
- Pfizer (AG024904, W81XWH-12-2-0012, U01 AG024904)
- GlaxoSmithKline
- Massachusetts General Hospital
- Biogen (W81XWH-12-2-0012, U01 AG024904, AG024904)
- University of Southern California (W81XWH-12-2-0012, U01 AG024904)
- F. Hoffmann-La Roche (W81XWH-12-2-0012, AG024904, U01 AG024904)
- Medpace (U01 AG024904)
- Meso Scale Diagnostics (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Stanley Medical Research Institute
- Synarc (U01 AG024904)
- Harvard University
- Alzheimer's Disease Neuroimaging Initiative (W81XWH-12-2–0012, U01AG024904, AG024904, W81XWH-12-2-)
- Strategiske Forskningsråd
- Aarhus Universitet
- BioClinica (U01 AG024904, W81XWH-12-2-0012, AG024904)
- Johns Hopkins University
- Novartis Pharmaceuticals Corporation (W81XWH-12-2-0012, U01 AG024904, AG024904)
- Højteknologifonden
- Sylvia and Charles Viertel Charitable Foundation (386500)
- NHS Blood and Transplant
- National Alliance for Research on Schizophrenia and Depression (603016, U54 EB020403, P41 EB015922, 602805)
- Northern California Institute for Research and Education (U01 AG024904, W81XWH-12-2-0012)
- Wellcome Trust (085475/Z/08/Z, 068545/Z/02), FP7/2007–2013, 602450, 068545/Z/0, 251704, 076113/CI04/Z, 085475, WT0618S8, 084710, G0000934, 075491/Z/04/Z, U54 EB020403, WT 083948/Z/07/Z, 068545, 072894/Z/03/Z, 075491/Z/04,, 104036, 100309/A/12/Z, 090532, 242167, 085475/B/08/Z, 223273, 090532/Z/09/Z, 090532/Z/09/, 076113, 076113/C/04/Z, 090532/Z, 083948)
- Pratt Foundation (386500)
- Broad Institute (R01 MH084098)
- Australian Government
- Max-Planck-Förderstiftung
- National Institute for Health and Care Research (R01 MH077139, FP7/2007–2013, G0000934, RP-PG-0310-1002, 619667, U01 AG024904, U54 EB020403, 090532/Z/09/Z., 278948, PG-0310-1002)
- British Heart Foundation
- Scottish Funding Council
- British Medical Association
- European Commission (242257, U01 AG024904, 090532/Z/09/Z, 313010, EU-FP7, 602450, 2007–2013, SF0180142s08, U54 EB020403, U01 MH081928, 230374, 01ZZ0103, FP7 2007-2013, 278948, 279227, 115300, 1RC2 MH089995, 218251, 286213, FP7/2007, 34,35, 01ZZ0403, W81XWH-12-2-0012, 242167, 03ZIK012, 28,29, 01ZZ9603, 603016, 57,58, 241909, LSHMCT-2007-037286, 602805)
- Commonwealth Scientific and Industrial Research Organisation
- Agency for Science, Technology and Research
- Science Foundation Ireland (08/IN.1/B1916, LSHM-CT-2007-037286, U54 EB020403)
- Deutsche Forschungsgemeinschaft (Gr1912/5‐1, U54 EB020403, 01ZZ0403, 602805, FP7/2007–2013, 01ZZ9603, 03ZIK012, 01ZZ0103)
- Universiteit Leiden (10‐000‐1002)
- University of New South Wales
- University of Melbourne (401184, 310667)
- ZonMw (400-07-080, 56-464-14192, 1RC2 MH089995, 480‐04‐004, 10‐000‐1002)
- Universiteit Utrecht
- Radboud Universiteit
- Vrije Universiteit Amsterdam (FP7/2007-2013, 278948)
- Svenska Forskningsrådet Formas (115300, 345-2003-3883, 315-2004-6977)
- Academy of Finland (W81XWH-12-2-0012, 251704, U01 AG024904)
- Bundesministerium für Bildung und Forschung (01GS0481, 01ZZ9603, 01ZZ0103, and 01ZZ0403, 01GS08148, 1EV0711, 01ZX1311A, 01ZX1314C, eMED SysAlc01ZX1311A, 01ZX1314G, U54 EB020403, 01GS08147, 03ZIK012, 01ZZ0403, and 01ZZ0403, 12,13, 01GS08144, FKZ 01GS0481, 01ZZ0103, 01ZX1314A, 01ZZ9603)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (10-000-1002, NWO 480‐05‐003, NWO/ SPI 56-464-14192, 13770, 480- 05-003, 602805, 175.010.2007.010, MW 904-61-193, FP7 2007-2013, 56‐464‐14192, 602450, 016‐130‐669, 230374, 01ZZ9603, 603016, 01ZZ0403, 400-07- 080, 433‐09‐220, 668-772, Spi-56-464-14192, 278948, 14192, 480-04-004, MaGW-nr: 400-07-080, MagW 480-04-004, 51.02.060, 1RC2 MH089995, 01ZZ0103)
- Accare
- Lundbeckfonden (R155-2014-1724, R24-A3243)
- Eisai (W81XWH-12-2-0012, U01 AG024904, AG024904)
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Max-Planck-Gesellschaft
- Stockholms Läns Landsting
- Vetenskapsrådet (70374401, FP7/2007-2013, 345-2003-3883; 315-2004-6977, U54 RR020278, 345-2003-3883, 80576801, 2006-4472, R01 MH077139, 315‐2004‐6977, 2009-05269)
- Riksbankens Jubileumsfond
- Universitetet i Bergen (223273)
- Leids Universitair Medisch Centrum
- Universitair Medisch Centrum Groningen
- Alfried Krupp von Bohlen und Halbach-Stiftung
- Norges Forskningsråd ((#217776, 242167, 223273, 213837, 2013-123, 230374)
- Akademiska Sjukhuset
- Radboud Universitair Medisch Centrum
- Centre d'Imagerie BioMédicale (R01 EB008432)
- Bergens Forskningsstiftelse
- Uppsala Universitet
- Tartu Ülikool (SP1GVARENG)
- Hersenstichting
- Science for Life Laboratory
- Servier (AG024904, W81XWH-12-2-0012, U01 AG024904)
- H. Lundbeck A/S (U01 AG024904, AG024904, W81XWH-12-2-0012)
- Ramsay Health Care (386500)
- IXICO (AG024904, W81XWH-12-2-0012, U01 AG024904)
- Australian Schizophrenia Research Bank (386500)
- Universität Greifswald
- Max Planck Instituut voor Psycholinguïstiek
- National Institutes of Health (3u01ag024904-10s2, NMRC/TCR/003/2008, R01D0042157-01A, 486682, G0000934, FP7/2007-2013, NWO/SPI 56-464-14192, 389875, 223273, NIMH K01, 1009064, 2013-123, NIH-R01, 075491/Z/04, ERC 230374, W81XWH, 6u54rr020278-06, 068545/Z/02, W81XWH-12-2-0012, 213837, 10,11, 1r01mh081802-01, EB015922, U01-AG024904, AG024904, EB020403)
- Genentech (W81XWH-12-2-0012, AG024904, U01 AG024904)
- University of California, San Diego
- Seventh Framework Programme (286213, FP7/2007, 115300, EU-FP7, 603016, FP7/2007 - 2013, U01 MH081928, 279227, 602805, 242167, 313010, 278948, 602450, 2007‐2013, HEALTH-F2-2010–241909)
- Stanley Center for Psychiatric Research, Broad Institute
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital
- Canadian Institutes of Health Research (U01 AG024904, W81XWH-12-2-0012)
- Medical Research Council (FP7/20072013, MR/L023784/2, MR/K026992/1, 115300, LSHM-CT-2007-037286, 350833, U01 AG024904, G0801418, MR/P005748/1, 93558, MR/L016400/1, 068545/Z/02, G0000934, MR/L010305/1, 090532/Z09/Z, U54 EB020403, G0800509, EU FP7)
- Australian Research Council (568969, FT110100548, 1045325, 389875, 401162, FT0991634, 350833)
- National Health and Medical Research Council (568969, 386500, 568940, 525453, 401162, 619667, 310667, EB008432, 1009064, 486682, R01 HD050735, 389875, 1045325, 401184, 350833, G0000934)
- National Medical Research Council (NMRC/TCR/003/2008, NMRC/TCR/003)
- European Regional Development Fund (FP7/2007‐2013, CZ.2.16/3.1, CZ.2.16/3.1.00/24022OPPK, 2007 – 2013, 3.2.0304.11-0312)
- Strategic Research Council
- Biomedical Research Council
- National Institute on Aging (U01-AG-024904, P30AG010129, R01AG040060, R01AG054076, R01AG033193, R01AG008122, U24AG021886)
- National Institute of Mental Health (U01 AG024904, MH59566, K23MH001760, R01MH041953, K99MH102357, R01MH068922, R01MH062276, MH-60870, MH 085667, R01MH077139, MH080272, R01MH092380, MH100141, MH001760, MH094421, MH085542, RC2MH089964, NIMHR01, MH 52618, MH089722, U01MH046276, MH089964, U01MH109528, MH071681, R01MH100141, MH-081802, MH095034, P50MH080272, MH-59586, R01MH061884, U01MH085520, R01MH059566, MH79470, MH60879, R01MH052618, MH097268, W81XWH-12-2-0012, U01MH046318, MH81800, MH041953, R01MH059571, R01MH058693, MH-083094, MH 61675, RC2MH089995, U01MH081928, MH41953, R01MH060879, MH089951, R01MH059565, MH67257, R01MH085667, MH46289, R01MH081800, R01MH085542, MH094343, MH46318, R01MH060870, R01MH097268, U01MH094421, U01MH046289, MH-068881, U01MH079469, MH085548, K01MH085812, K99MH101367, R01MH061675, R01MH078075, R01MH094343, MH065580, R01MH062873, MH084098, R01MH085548, R00MH102357, R01MH059586, R01MH071681, MH58693, R01MH083094, MH59571, R01MH059588, K01MH065580, R01MH067257, U01MH079470, MH085812, MH59588, MH79469, MH078075, MH-59587, NMRC/TCR/003/2008, MH59565, 115300, R01MH095034, RC2MH089951, MH077139, R01MH068881, MH081928, R01 MH081802, MH061884, K01MH099232, R01MH084098, R01MH059587, MH089995, K24MH094614, MH-46276, R01MH068921, R01MH089722)
- National Cancer Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK075787)
- National Institute of Neurological Disorders and Stroke (R01NS080655)
- National Institute of Biomedical Imaging and Bioengineering (R01EB020407, W81XWH-12-2-0012, R01EB008432, R01EB005846, EB015922, U01 AG024904, U54EB020403, EB008432, P41EB015922, R01EB006841, AG024904)
- National Center for Research Resources (U54-RR020278, RR026075, MH097268, U01 AG024904, RR020278)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD050735)
- Scottish Mental Health Research Network
- FP7 Ideas: European Research Council (268800)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, subcortical volume, genetic overlap, common genetic variants, brain imaging phenotypes, mental illness, genetic covariance, psychiatric genetics
- MeSH terms
- Brain, Humans, Magnetic Resonance Imaging, Organ Size, Schizophrenia, Linkage Disequilibrium, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Endophenotypes, Neuroimaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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