Johnson, Emma C., 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. ORCID: https://orcid.org/0000-0001-7073-2379, Walters, James T. R. ORCID: https://orcid.org/0000-0002-6980-4053, Gelernter, Joel, Edenberg, Howard J. and Agrawal, Arpana 2023. Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder. Psychological Medicine 53 (4) , pp. 1196-1204. 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 |
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Date Type: | Publication |
Status: | Published |
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: | 17 Nov 2024 07:15 |
URI: | https://orca.cardiff.ac.uk/id/eprint/142137 |
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