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; Psychiat Genomics Consortium; ENIGMA 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, Psychiat Genomics Consortium, ENIGMA Consortium

^*Corresponding author for this work

Applied Medicine

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

164 Citations (Scopus)

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
Early online date	1 Feb 2016
DOIs	https://doi.org/10.1038/nn.4228
Publication status	Published - Mar 2016

Keywords

GENOME-WIDE ASSOCIATION
METAANALYSIS
ENDOPHENOTYPE
INDIVIDUALS
PERSPECTIVE
PHENOTYPES
DISORDERS
DISCOVERY
RELATIVES
VARIANTS

Access to Document

10.1038/nn.4228Licence: Unspecified

Cite this

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., ... ENIGMA 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

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, Psychiat Genomics Consortium & ENIGMA Consortium 2016, 'Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept', Nature Neuroscience, vol. 19, no. 3, pp. 420-431. https://doi.org/10.1038/nn.4228

@article{6770b5c7a6274fb39192eb128c19ae9f,

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 {Psychiat Genomics Consortium} and {ENIGMA Consortium} and {St Clair}, {David Malcolm} and Pike, {G. Bruce}",

year = "2016",

month = mar,

doi = "10.1038/nn.4228",

language = "English",

volume = "19",

pages = "420--431",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Publishing Group",

number = "3",

}

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 - Psychiat Genomics Consortium

AU - ENIGMA Consortium

AU - St Clair, David Malcolm

AU - Pike, G. Bruce

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this