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

Barbara Franke; Jason L. Stein; Stephan Ripke; Verneri Anttila; Derrek P. Hibar; Kimm J. E. van Hulzen; Alejandro Arias-Vasquez; Jordan W. Smoller; Thomas E. Nichols; Michael C. Neale; Andrew M. McIntosh; Phil Lee; Francis J. McMahon; Andreas Meyer-Lindenberg; Manuel Mattheisen; Ole A. Andreassen; Oliver Gruber; Perminder S. Sachdev; Roberto Roiz-Santianez; Andrew J. Saykin; Stefan Ehrlich; Karen A. Mather; Jessica A. Turner; Margaret J. Wright; Michael C. O'Donovan; Paul M. Thompson; Benjamin M. Neale; Sarah E. Medland; Patrick F. Sullivan; ENIGMA Consortium; Psychiat Genomics Consortium

doi:10.1038/nn.4228

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

Barbara Franke, Jason L. Stein, Stephan Ripke, Verneri Anttila, Derrek P. Hibar, Kimm J. E. van Hulzen, Alejandro Arias-Vasquez, Jordan W. Smoller, Thomas E. Nichols, Michael C. Neale, Andrew M. McIntosh, Phil Lee, Francis J. McMahon, Andreas Meyer-Lindenberg, Manuel Mattheisen, Ole A. Andreassen, Oliver Gruber, Perminder S. Sachdev, Roberto Roiz-Santianez, Andrew J. SaykinStefan Ehrlich, Karen A. Mather, Jessica A. Turner, Margaret J. Wright, Michael C. O'Donovan, Paul M. Thompson, Benjamin M. Neale, Sarah E. Medland, Patrick F. Sullivan, ENIGMA Consortium, Psychiat Genomics Consortium

Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Onderzoeksoutput › Academic › peer review

171 Citaten (Scopus)

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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.

Originele taal-2	English
Pagina's (van-tot)	420-431
Aantal pagina's	12
Tijdschrift	Nature neuroscience
Volume	19
Nummer van het tijdschrift	3
DOI's	https://doi.org/10.1038/nn.4228
Status	Published - mrt.-2016

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Franke, B., 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-Santianez, R., ... Psychiat Genomics Consortium (2016). Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept. Nature neuroscience, 19(3), 420-431. https://doi.org/10.1038/nn.4228

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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.",

keywords = "GENOME-WIDE ASSOCIATION, METAANALYSIS, ENDOPHENOTYPE, INDIVIDUALS, PERSPECTIVE, PHENOTYPES, DISORDERS, DISCOVERY, RELATIVES, VARIANTS",

author = "Barbara Franke and Stein, {Jason L.} and Stephan Ripke and Verneri Anttila and Hibar, {Derrek P.} and {van Hulzen}, {Kimm J. E.} and Alejandro Arias-Vasquez and Smoller, {Jordan W.} and Nichols, {Thomas E.} and Neale, {Michael C.} and McIntosh, {Andrew M.} and Phil Lee and McMahon, {Francis J.} and Andreas Meyer-Lindenberg and Manuel Mattheisen and Andreassen, {Ole A.} and Oliver Gruber and Sachdev, {Perminder S.} and Roberto Roiz-Santianez and Saykin, {Andrew J.} and Stefan Ehrlich and Mather, {Karen A.} and Turner, {Jessica A.} and Wright, {Margaret J.} and O'Donovan, {Michael C.} and Thompson, {Paul M.} and Neale, {Benjamin M.} and Medland, {Sarah E.} and Sullivan, {Patrick F.} and Hoekstra, {Pieter J.} and {ENIGMA Consortium} and {Psychiat Genomics Consortium}",

year = "2016",

month = mar,

doi = "10.1038/nn.4228",

language = "English",

volume = "19",

pages = "420--431",

journal = "Nature neuroscience",

issn = "1097-6256",

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number = "3",

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Franke, B, Stein, JL, Ripke, S, Anttila, V, Hibar, DP, van Hulzen, KJE, Arias-Vasquez, A, Smoller, JW, Nichols, TE, Neale, MC, McIntosh, AM, Lee, P, McMahon, FJ, Meyer-Lindenberg, A, Mattheisen, M, Andreassen, OA, Gruber, O, Sachdev, PS, Roiz-Santianez, R, Saykin, AJ, Ehrlich, S, Mather, KA, Turner, JA, Wright, MJ, O'Donovan, MC, Thompson, PM, Neale, BM, Medland, SE, Sullivan, PF, ENIGMA Consortium & Psychiat Genomics Consortium 2016, 'Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept', Nature neuroscience, vol. 19, nr. 3, blz. 420-431. https://doi.org/10.1038/nn.4228

TY - JOUR

T1 - Genetic influences on schizophrenia and subcortical brain volumes

T2 - large-scale proof of concept

AU - Franke, Barbara

AU - Stein, Jason L.

AU - Ripke, Stephan

AU - Anttila, Verneri

AU - Hibar, Derrek P.

AU - van Hulzen, Kimm J. E.

AU - Arias-Vasquez, Alejandro

AU - Smoller, Jordan W.

AU - Nichols, Thomas E.

AU - Neale, Michael C.

AU - McIntosh, Andrew M.

AU - Lee, Phil

AU - McMahon, Francis J.

AU - Meyer-Lindenberg, Andreas

AU - Mattheisen, Manuel

AU - Andreassen, Ole A.

AU - Gruber, Oliver

AU - Sachdev, Perminder S.

AU - Roiz-Santianez, Roberto

AU - Saykin, Andrew J.

AU - Ehrlich, Stefan

AU - Mather, Karen A.

AU - Turner, Jessica A.

AU - Wright, Margaret J.

AU - O'Donovan, Michael C.

AU - Thompson, Paul M.

AU - Neale, Benjamin M.

AU - Medland, Sarah E.

AU - Sullivan, Patrick F.

AU - Hoekstra, Pieter J.

AU - ENIGMA Consortium

AU - Psychiat Genomics Consortium

PY - 2016/3

Y1 - 2016/3

N2 - 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.

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.

KW - GENOME-WIDE ASSOCIATION

KW - METAANALYSIS

KW - ENDOPHENOTYPE

KW - INDIVIDUALS

KW - PERSPECTIVE

KW - PHENOTYPES

KW - DISORDERS

KW - DISCOVERY

KW - RELATIVES

KW - VARIANTS

U2 - 10.1038/nn.4228

DO - 10.1038/nn.4228

M3 - Article

SN - 1097-6256

VL - 19

SP - 420

EP - 431

JO - Nature neuroscience

JF - Nature neuroscience

IS - 3

ER -

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

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