Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia

V. Bansal; Marina Mitjans; Casper A.P. Burik; Richard Karlsson Linnér; Aysu Okbay; Cornelius A. Rietveld; Martin Begemann; Stefan Bonn; Stephan Ripke; Ronald de Vlaming; Michel Guillaume Nivard; Hannelore Ehrenreich; Philipp Koellinger

doi:10.1038/s41467-018-05510-z

GeneticsNature CommunicationsJul 31, 2018

Peer-reviewed journal article

Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia

V. Bansal iD, Marina Mitjans iD, Casper A.P. Burik iD, Richard Karlsson Linnér iD, Aysu Okbay iD, Cornelius A. Rietveld iD, Martin Begemann iD, Stefan Bonn iD, Stephan Ripke iD, Ronald de Vlaming iD, Michel Guillaume Nivard iD, Hannelore Ehrenreich iD, Philipp Koellinger iD

Abstract

Higher educational attainment (EA) is negatively associated with schizophrenia (SZ). However, recent studies found a positive genetic correlation between EA and SZ. We investigated possible causes of this counterintuitive finding using genome-wide association study results for EA and SZ (N = 443,581) and a replication cohort (1,169 controls; 1,067 cases) with deeply phenotyped SZ patients. We found strong genetic dependence between EA and SZ that cannot be explained by chance, linkage disequilibrium, or assortative mating. Instead, several genes seem to have pleiotropic effects on EA and SZ, but without a clear pattern of sign concordance. Genetic heterogeneity of SZ contributes to this finding. We demonstrate this by showing that the polygenic prediction of clinical SZ symptoms can be improved by taking the sign concordance of loci for EA and SZ into account. Furthermore, using EA as a proxy phenotype, we isolate FOXO6 and SLITRK1 as novel candidate genes for SZ.

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