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-Santiañez; Andrew J Saykin; Stefan Ehrlich; Karen A Mather; Jessica A Turner; Emanuel Schwarz; Anbupalam Thalamuthu; Yin Yao; Yvonne Y W Ho; Nicholas G Martin; Margaret J Wright; Schizophrenia Working Group of the Psychiatric Genomics Consortium; ENIGMA Consortium; Michael C O'Donovan; Paul M Thompson; Benjamin M Neale; Sarah E Medland; Patrick F Sullivan

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-Santiañez, Andrew J SaykinStefan Ehrlich, Karen A Mather, Jessica A Turner, Emanuel Schwarz, Anbupalam Thalamuthu, Yin Yao, Yvonne Y W Ho, Nicholas G Martin, Margaret J Wright, Schizophrenia Working Group of the Psychiatric Genomics Consortium, ENIGMA Consortium, Michael C O'Donovan, Paul M Thompson, Benjamin M Neale, Sarah E Medland, Patrick F Sullivan

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

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 - 31 Mar 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-Santiañez, R., ... Sullivan, P. F. (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.",

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-Santia{\~n}ez and Saykin, {Andrew J} and Stefan Ehrlich and Mather, {Karen A} and Turner, {Jessica A} and Emanuel Schwarz and Anbupalam Thalamuthu and Yin Yao and Ho, {Yvonne Y W} and Martin, {Nicholas G} and Wright, {Margaret J} and {Schizophrenia Working Group of the Psychiatric Genomics Consortium} and {ENIGMA Consortium} and O'Donovan, {Michael C} and Thompson, {Paul M} and Neale, {Benjamin M} and Medland, {Sarah E} and Sullivan, {Patrick F} and Lawrie, {Stephen M.} and Sussmann, {Jessika E.}",

year = "2016",

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doi = "10.1038/nn.4228",

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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-Santiañez, R, Saykin, AJ, Ehrlich, S, Mather, KA, Turner, JA, Schwarz, E, Thalamuthu, A, Yao, Y, Ho, YYW, Martin, NG, Wright, MJ, Schizophrenia Working Group of the Psychiatric Genomics Consortium, ENIGMA Consortium, O'Donovan, MC, Thompson, PM, Neale, BM, Medland, SE & Sullivan, PF 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

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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-Santiañez, Roberto

AU - Saykin, Andrew J

AU - Ehrlich, Stefan

AU - Mather, Karen A

AU - Turner, Jessica A

AU - Schwarz, Emanuel

AU - Thalamuthu, Anbupalam

AU - Yao, Yin

AU - Ho, Yvonne Y W

AU - Martin, Nicholas G

AU - Wright, Margaret J

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

AU - ENIGMA Consortium

AU - O'Donovan, Michael C

AU - Thompson, Paul M

AU - Neale, Benjamin M

AU - Medland, Sarah E

AU - Sullivan, Patrick F

A2 - Lawrie, Stephen M.

A2 - Sussmann, Jessika E.

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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.

U2 - 10.1038/nn.4228

DO - 10.1038/nn.4228

M3 - Article

C2 - 26854805

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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Stephen Lawrie

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

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