Journal Article

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

Meyer-Lindenberg, Andreas, Anttila, Verneri, van Hulzen, Kimm J E, Medland, Sarah E, Nichols, Thomas E, Mather, Karen A, Schwarz, Emanuel, Andreassen, Ole A, Thalamuthu, Anbupalam, Yao, Yin, Sachdev, Perminder S, Ehrlich, Stefan, Franke, Barbara, Ripke, Stephan, Ho, Yvonne Y W, Saykin, Andrew J, Wright, Margaret J, Martin, Nicholas G, O'Donovan, Michael C, Lee, Phil, McIntosh, Andrew M, Thompson, Paul M, Mattheisen, Manuel, Gruber, Oliver, Sullivan, Patrick F, Neale, Michael C, McMahon, Francis J, Roiz-Santiañez, Roberto, Hibar, Derrek P, Stein, Jason L, Arias-Vasquez, Alejandro, Smoller, Jordan W, Neale, Benjamin M, Turner, Jessica A

2016

Overview

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 45/43 / 631/1647/245/1628 / 631/208/205/2138 / 631/208/721 / 692/699/476/1799 / Animal Genetics and Genomics / Behavioral Sciences / Biological Techniques / Biomedicine / Brain - pathology / Cognitive science / Consortia / Disease susceptibility / Endophenotypes / Genetic aspects / Genetic Predisposition to Disease - genetics / Genome-wide association studies / Genome-Wide Association Study / Genomes / Health aspects / Health risk assessment / Humans / Identification and classification / Linkage Disequilibrium / Magnetic Resonance Imaging / Medical imaging / Mental disorders / Methods / Neurobiology / Neuroimaging / Neuroscience / Neurosciences / Organ Size / Phenotype / Polymorphism, Single Nucleotide - genetics / Schizophrenia / Schizophrenia - genetics / Schizophrenia - pathology