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

Johnson, Emma, Kapoor, Manav, Hatoum, Alexander S., Zhou, Hang, Polimanti, Renato, Wendt, Frank R., Walters, Raymond K., Lai, Dongbing, Kember, Rachel L., Hartz, Sarah, Meyers, Jacquelyn L., Peterson, Roseann E., Ripke, Stephan, Bigdeli, Tim B., Fanous, Ayman H., Pato, Carlos N., Goate, Alison M., Kranzler, Henry R., O'Donovan, Michael C., Walters, James T. R., Gelernter, Joel, Edenberg, Howard J. and Agrawal, Arpana 2021. Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder. Psychological Medicine 10.1017/S003329172100266X

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Abstract

Background Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders. Methods We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific. Results We identified 55 independent genome-wide significant single nucleotide polymorphisms 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). Conclusions Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Cambridge University Press
ISSN: 0033-2917
Date of First Compliant Deposit: 22 June 2021
Date of Acceptance: 14 June 2021
Last Modified: 07 Jan 2022 18:33
URI: https://orca.cardiff.ac.uk/id/eprint/142137

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