Nature neuroscience · 2022
Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction.
СтатьяМетаанализПоддержка правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Kember Rachel L, Vickers-Smith Rachel, Xu Heng, Toikumo Sylvanus, Niarchou Maria, Zhou Hang, Hartwell Emily E, Crist Richard C, Rentsch Christopher T, Million Veteran Program, Davis Lea K, Justice Amy C, Sanchez-Roige Sandra, Kampman Kyle M, Gelernter Joel, Kranzler Henry R
Аннотация
Despite an estimated heritability of ~50%, genome-wide association studies of opioid use disorder (OUD) have revealed few genome-wide significant loci. We conducted a cross-ancestry meta-analysis of OUD in the Million Veteran Program (N = 425,944). In addition to known exonic variants in OPRM1 and FURIN, we identified intronic variants in RABEPK, FBXW4, NCAM1 and KCNN1. A meta-analysis including other datasets identified a locus in TSNARE1. In total, we identified 14 loci for OUD, 12 of which are novel. Significant genetic correlations were identified for 127 traits, including psychiatric disorders and other substance use-related traits. The only significantly enriched cell-type group was CNS, with gene expression enrichment in brain regions previously associated with substance use disorders. These findings increase our understanding of the biological basis of OUD and provide further evidence that it is a brain disease, which may help to reduce stigma and inform efforts to address the opioid epidemic.