Genetic influences on schizophrenia and subcortical brain volumes: Large-scale proof of concept

Psychosis Endophenotypes International Consortium

doi:10.1038/nn.4228

Genetic influences on schizophrenia and subcortical brain volumes: Large-scale proof of concept

Psychosis Endophenotypes International Consortium

Research output: Contribution to journal › Article › peer-review

167 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	420-431
Number of pages	12
Journal	Nature Neuroscience
Volume	19
Issue number	3
DOIs	https://doi.org/10.1038/nn.4228
State	Published - 23 Feb 2016
Externally published	Yes

Funding

Funders	Funder number
Centre for Medical Systems Biology
National Institute of Child Health and Human Development
Australian Government
Leids Universitair Medisch Centrum
Welsh Assembly Government
K.G. Jebsen Foundation
FP7 projects IMAGEMEND
Biobanking and Biomolecular Resources Research Infrastructure
Federal State of Mecklenburg
Aarhus Universitet
Svenska Forskningsrådet Formas
MATRICS
German Ministry of Cultural Affairs
Lundbeckfonden
EU-GEI
National Institute for Health Research
Stanley Foundation
Max-Planck-Gesellschaft
Max-Planck-Förderstiftung
North Shore – Long Island Jewish Health System Foundation
Radboud Universitair Medisch Centrum
Stanley Research Foundation
Dr Einar Martens Fund
Vrije Universiteit Amsterdam
BBMRI-NL
National Health and Medical Research Council
Strategiske Forskningsråd
Dutch Brain Foundation
Seventh Framework Programme
High Potential Grant Utrecht University
Neuroscience Campus Amsterdam
Universitetet i Bergen
VU University’s Institutes for Health and Care Research
Netherlands Organization for Health Research and Development
British Medical Association
Donald and Barbara Zucker Foundation
Janssen Research Foundation
U.S. Department of Veterans Affairs
European Research Council
Vetenskapsrådet
NIHR Biomedical Research Center
Commonwealth Scientific and Industrial Research Organisation Flagship Collaboration Fund
ZonMw	R01 MH078075
ZonMw
Seventh Framework Programme	268800, 242257, 602805, 242167, 286213, MW904-61-193, 218251, 313010, MagW 480-04-004, NWO/SPI 56-464-14192, 51.02.060, HEALTH-F2-2010-241909, 241909, 115300, 230374, 602450, 279227, 278948, MaGW-nr 400-07-080, 668.772, 603016
Seventh Framework Programme
Dementia Australia Research Foundation	P41 EB015922, R01NS080655, R01AG040060, R01 MH089722, U01 AG024904, R01MH085667, 568940, R01 MH097268, R01 MH094343, R01 EB008432
Dementia Australia Research Foundation
National Institute of Mental Health	K01MH085812, R01MH061884, R01MH059566, R01MH060870, R01MH059565, K24MH094614, U01MH085520, RC2MH089964, R01MH060879, R01MH092380, R01MH041953, U01MH046289, R01MH052618, K23MH001760, R01MH059571, R01MH068921, K99MH102357, R01MH068922, R01MH089722, K01MH099232, RC2MH089951, RC2MH089995, R01MH078075, R01MH081802, R01MH071681, R01MH081800, U01MH046276, U01MH081928, P50MH080272, R01MH068881, U01MH046318, R01MH062276, R01MH062873, R01MH058693, R01MH059586, U01MH079469, R01MH059588, R01MH059587, R01MH094343, R01MH095034, R01MH077139, K01MH065580, R01MH097268, U01MH094421, U01MH109528, R01MH083094, R01MH084098, K99MH101367, R01MH061675, R01MH085542, R01MH067257, R01MH085667, ZIAMH002810, R01MH085548, R01MH100141, U01MH079470
National Institute of Mental Health
Medical Research Council	MC_UU_12013/2, G0000934, MC_UU_12013/1, G0801418, G0901858, 93558, G0800509, G1100616, MR/L010305/1, MR/K026992/1, MR/L016400/1, MR/P005748/1
Medical Research Council
National Center for Research Resources	U54RR020278, RR026075
National Center for Research Resources
European Union-funded FP6	LSHM-CT-2007-037286
EU-AIMS	115300-2
National Institute of Neurological Disorders and Stroke	R01NS080655
National Institute of Neurological Disorders and Stroke
NHS Blood and Transplant	RP-PG-0310-1002, WTCCC-084710, R01 MH068881, R01 MH083094, R01 MH041953
NHS Blood and Transplant
BiG Grid	1750102007010, R01MH62873
Norges Forskningsråd	217776, 223273, 213837
Norges Forskningsråd
HelmholtzZentrum München	568969, 350833, 03ZIK012
National Science Foundation	1229450
National Science Foundation
Bundesministerium für Bildung und Forschung	01GS08144, 01GS08147, 01ZX1314G, 01GS08148, 01ZX1314A, 01ZX1314C, 1EV0711
Bundesministerium für Bildung und Forschung
National Institute of Biomedical Imaging and Bioengineering	P41EB015922, R01EB005846, R01EB008432, U54EB020403
National Institute of Biomedical Imaging and Bioengineering
Australian Research Council	310667, 1045325, 401162
Australian Research Council
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	480-05-003, 10-000-1002
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
National Alliance for Research on Schizophrenia and Depression	MH001760, MH065580
National Alliance for Research on Schizophrenia and Depression
University of New South Wales	525453
University of New South Wales
National Institute on Aging	U24AG021886, R01AG033193, U01AG024904, R01AG040060, R01AG054076, R01AG008122
National Institute on Aging
National Institutes of Health	R01D0042157-01A
National Institutes of Health
Eunice Kennedy Shriver National Institute of Child Health and Human Development	R01HD050735
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Exzellenz-Stiftung of the Max Planck Society	FKZ 01GS0481
University of Melbourne	401184
University of Melbourne
Deutsche Forschungsgemeinschaft	GR 1912/5-1
Deutsche Forschungsgemeinschaft
Horizon 2020 Framework Programme	692145
Horizon 2020 Framework Programme
Wellcome Trust	076113/C/04/Z, 068545/Z/0
Wellcome Trust
Autism Speaks	01ZZ0403, FT110100548, 486682, 389875, FT0991634, 619667, R01 HD050735, 01ZZ9603, 01ZZ0103, 1009064
Autism Speaks
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK075787
National Institute of Diabetes and Digestive and Kidney Diseases
Massachusetts General Hospital Executive Committee on Research	MH085542, K99 MH101367, MH071681, MH085548, MH061884
South-East Norway Health Authority	2013-123
National Institutes of Health	R01MH084098, R01MH085542, P50MH080272
National Institutes of Health

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10.1038/nn.4228

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@article{a04ef56572e64395ad2686968a7f9294,

title = "Genetic influences on schizophrenia and subcortical brain volumes: Large-scale proof of concept",

abstract = "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.",

author = "{Psychosis Endophenotypes International Consortium} and Barbara Franke and {van Hulzen}, {Kimm J.E.} and Alejandro Arias-Vasquez and Janita Bralten and Martine Hoogman and Marieke Klein and {van Donkelaar}, {Marjolein M.J.} and Hakobjan, {Marina M.H.} and Heister, {Angelien J.G.A.M.} and Makkinje, {Remco R.R.} and Naber, {Marlies A.M.} and {van der Marel}, {Saskia S.L.} and Mostert, {Jeanette C.} and Brunner, {Han G.} and {van Bokhoven}, Hans and Zwiers, {Marcel P.} and Buitelaar, {Jan K.} and Guill{\'e}n Fern{\'a}ndez and Fisher, {Simon E.} and Clyde Francks and Stein, {Jason L.} and Hibar, {Derrek P.} and Thompson, {Paul M.} and Stephan Ripke and Verneri Anttila and Neale, {Benjamin M.} and Farh, {Kai How} and Brendan Bulik-Sullivan and Hailiang Huang and Menachem Fromer and Goldstein, {Jacqueline I.} and Daly, {Mark J.} and Walters, {Raymond K.} and Smoller, {Jordan W.} and Phil Lee and Belliveau, {Richard A.} and Bergen, {Sarah E.} and Elizabeth Bevilacqua and Chambert, {Kimberley D.} and Giulio Genovese and Colm O'Dushlaine and Scolnick, {Edward M.} and McCarroll, {Steven A.} and Moran, {Jennifer L.} and Aarno Palotie and Petryshen, {Tracey L.} and Susanne Erk and Andreas Heinz and Michael Davidson and Mark Weiser",

year = "2016",

month = feb,

day = "23",

doi = "10.1038/nn.4228",

language = "אנגלית",

volume = "19",

pages = "420--431",

journal = "Nature Neuroscience",

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AU - Franke, Barbara

AU - van Hulzen, Kimm J.E.

AU - Arias-Vasquez, Alejandro

AU - Bralten, Janita

AU - Hoogman, Martine

AU - Klein, Marieke

AU - van Donkelaar, Marjolein M.J.

AU - Hakobjan, Marina M.H.

AU - Heister, Angelien J.G.A.M.

AU - Makkinje, Remco R.R.

AU - Naber, Marlies A.M.

AU - van der Marel, Saskia S.L.

AU - Mostert, Jeanette C.

AU - Brunner, Han G.

AU - van Bokhoven, Hans

AU - Zwiers, Marcel P.

AU - Buitelaar, Jan K.

AU - Fernández, Guillén

AU - Fisher, Simon E.

AU - Francks, Clyde

AU - Stein, Jason L.

AU - Hibar, Derrek P.

AU - Thompson, Paul M.

AU - Ripke, Stephan

AU - Anttila, Verneri

AU - Neale, Benjamin M.

AU - Farh, Kai How

AU - Bulik-Sullivan, Brendan

AU - Huang, Hailiang

AU - Fromer, Menachem

AU - Goldstein, Jacqueline I.

AU - Daly, Mark J.

AU - Walters, Raymond K.

AU - Smoller, Jordan W.

AU - Lee, Phil

AU - Belliveau, Richard A.

AU - Bergen, Sarah E.

AU - Bevilacqua, Elizabeth

AU - Chambert, Kimberley D.

AU - Genovese, Giulio

AU - O'Dushlaine, Colm

AU - Scolnick, Edward M.

AU - McCarroll, Steven A.

AU - Moran, Jennifer L.

AU - Palotie, Aarno

AU - Petryshen, Tracey L.

AU - Erk, Susanne

AU - Heinz, Andreas

AU - Davidson, Michael

AU - Weiser, Mark

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AB - 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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JF - Nature Neuroscience

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ER -

Genetic influences on schizophrenia and subcortical brain volumes: Large-scale proof of concept

Abstract

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