Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder

Emma C. Johnson; Manav Kapoor; Alexander Samir Hatoum; Hang Zhou; Renato A Polimanti; Frank R. Wendt; Raymond Kenney Walters; Dongbing Lai; Rachel L. Kember; Sarah M. Hartz; Jacquelyn Leigh Meyers; Roseann Elizabeth Peterson; Stephan Ripke; Tim B. Bigdeli; Ayman H. Fanous; Carlos N. Pato; Michele T. Pato; Alison Goate; Henry R. Kranzler; Michael C. O’Donovan; James Walters; Joel E. Gelernter; Howard J. Edenberg; Arpana Agrawal A

doi:10.1017/s003329172100266x

Genetic & Genomic MedicinePsychological MedicineJul 7, 2021

Peer-reviewed journal article

Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder

Emma C. Johnson iD, Manav Kapoor iD, Alexander Samir Hatoum iD, Hang Zhou iD, Renato A Polimanti iD, Frank R. Wendt iD, Raymond Kenney Walters iD, Dongbing Lai iD, Rachel L. Kember iD, Sarah M. Hartz iD, Jacquelyn Leigh Meyers iD, Roseann Elizabeth Peterson iD, Stephan Ripke iD, Tim B. Bigdeli iD, Ayman H. Fanous iD, Carlos N. Pato iD, Michele T. Pato iD, Alison Goate iD, Henry R. Kranzler iD, Michael C. O’Donovan iD, James Walters iD, Joel E. Gelernter iD, Howard J. Edenberg iD, Arpana Agrawal A iD

Abstract

BackgroundAlcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and recent genome-wide association studies (GWAS) have identified significant genetic correlations between them. MethodsWe used the largest published GWAS for AUD (total cases = 77,822) and SCZ (total cases = 46,827) to systematically identify genetic variants that influence both disorders (in either the same or opposite direction of effect) as well as disorder-specific loci. ResultsWe identified 55 independent genome-wide significant SNPs with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001). ConclusionsOur findings provide further evidence that SCZ shares meaningful genetic overlap with AUD, and suggest that genetic variants with an effect on both disorders are expressed in brain tissues.

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