Abstract

Higher educational attainment (EA) is negatively associated with schizophrenia (SZ). However, recent studies found a positive genetic correlation between EA and SZ. We investigate possible causes of this counterintuitive finding using genome-wide association study results for EA and SZ (N = 443,581) and a replication cohort (1169 controls; 1067 cases) with deeply phenotyped SZ patients. We find 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. Using EA as a proxy phenotype, we isolate FOXO6 and SLITRK1 as novel candidate genes for SZ. Our results reveal that current SZ diagnoses aggregate over at least two disease subtypes: one part resembles high intelligence and bipolar disorder (BIP), while the other part is a cognitive disorder that is independent of BIP.

Details

Title
Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia
Author
Bansal, V 1   VIAFID ORCID Logo  ; Mitjans, M 2 ; Burik, C A P 3 ; Linnér, R K 3   VIAFID ORCID Logo  ; Okbay, A 4   VIAFID ORCID Logo  ; Rietveld, C A 5 ; Begemann, M 6 ; Bonn, S 7   VIAFID ORCID Logo  ; Ripke, S 8 ; de Vlaming, R 4   VIAFID ORCID Logo  ; Nivard, M G 9   VIAFID ORCID Logo  ; Ehrenreich, H 2 ; Koellinger, P D 3 

1  Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; Research Group for Computational Systems Biology, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany; Institute of Medical Systems Biology, Center for Molecular Neurobiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany 
2  Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany 
3  Complex Trait Genetics, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, Netherlands; School of Business and Economics, Department of Economics, Amsterdam, Netherlands 
4  Complex Trait Genetics, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; School of Business and Economics, Department of Economics, Amsterdam, Netherlands 
5  Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, Netherlands; Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, Netherlands 
6  Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany; Department of Psychiatry & Psychotherapy, University of Göttingen, Göttingen, Germany 
7  Research Group for Computational Systems Biology, German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany; Institute of Medical Systems Biology, Center for Molecular Neurobiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany 
8  Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA; Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany 
9  Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands 
Pages
1-12
Publication year
2018
Publication date
Aug 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-05510-z
ProQuest document ID
2084328563
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.