Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder
| Autor: | Howard J. Edenberg, Alison Goate, Manav Kapoor, Michael Conlon O'Donovan, Tim B. Bigdeli, Dongbing Lai, Ayman H. Fanous, Henry R. Kranzler, Hang Zhou, James T.R. Walters, Emma C. Johnson, Sarah M. Hartz, Renato Polimanti, Jacquelyn L. Meyers, Carlos N. Pato, Alexander S. Hatoum, Roseann E. Peterson, Joel Gelernter, Raymond K. Walters, Stephan Ripke, Frank R. Wendt, Arpana Agrawal, Rachel L. Kember, Michele T. Pato |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genetics Mediation (statistics) Genome-wide association study Single-nucleotide polymorphism Alcohol use disorder Biology medicine.disease Article 03 medical and health sciences Psychiatry and Mental health 030104 developmental biology 0302 clinical medicine Schizophrenia Pleiotropy mental disorders medicine Prefrontal cortex 030217 neurology & neurosurgery Applied Psychology Genetic association |
| Zdroj: | Psychol Med |
| ISSN: | 1469-8978 0033-2917 |
| DOI: | 10.1017/s003329172100266x |
| Popis: | BackgroundAlcohol 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.MethodsWe 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.ResultsWe 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).ConclusionsOur findings provide further evidence that SCZ shares meaningful genetic overlap with AUD. |
| Databáze: | OpenAIRE |
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