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- W3177792764 abstract "Abstract Stimulant dependence is heritable, but specific genetic factors underlying the trait have not been identified. A genome-wide association study for stimulant dependence was performed in a discovery cohort of African- (AA) and European-ancestry (EA) subjects ascertained for genetic studies of alcohol, opioid, and cocaine use disorders. The sample comprised individuals with DSM-IV stimulant dependence (393 EA cases, 5288 EA controls; 155 AA cases, 5603 AA controls). An independent cohort from the family-based Collaborative Study on the Genetics of Alcoholism (532 EA cases, 7635 EA controls; 53 AA cases, AA 3352 controls) was used for replication. One variant in SLC25A16 (rs2394476, p = 3.42 × 10 −10 , odds ratio [OR] = 3.70) was GWS in AAs. Four other loci showed suggestive evidence, including KCNA4 in AAs (rs11500237, p = 2.99 × 10 −7 , OR = 2.31) which encodes one of the potassium voltage-gated channel protein that has been linked to several other substance use disorders, and CPVL in the combined population groups (rs1176440, p = 3.05 × 10 −7 , OR = 1.35), whose expression was previously shown to be upregulated in the prefrontal cortex from users of cocaine, cannabis, and phencyclidine. Analysis of the top GWAS signals revealed a significant enrichment with nicotinic acetylcholine receptor genes (adjusted p = 0.04) and significant pleiotropy between stimulant dependence and alcohol dependence in EAs ( p adj = 3.6 × 10 −3 ), an anxiety disorder in EAs ( p adj = 2.1 × 10 −4 ), and ADHD in both AAs ( p adj = 3.0 × 10 −33 ) and EAs ( p adj = 6.7 × 10 −35 ). Our results implicate novel genes and pathways as having roles in the etiology of stimulant dependence." @default.
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- W3177792764 date "2021-06-29" @default.
- W3177792764 modified "2023-10-12" @default.
- W3177792764 title "Genome-wide association study of stimulant dependence" @default.
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- W3177792764 doi "https://doi.org/10.1038/s41398-021-01440-5" @default.
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