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Chunk #39 — Discussion

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Genome-wide association study of alcohol consumption and use disorder in 274,424 individuals from multiple populations.
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Both phenotypes showed cell type-specific enrichments for CNS. Other relevant cell types for AUDIT-C, but not for AUD, included cardiovascular, adrenal or pancreas, liver, and musculoskeletal. Thus, although heavy drinking is prerequisite to the development of AUD, the latter is a polygenic disorder and variation in genes expressed in the CNS (e.g., DRD2) may be necessary for individuals who drink heavily to develop AUD. As a binary trait, AUD provided less statistical power to identify genetic variation than the ordinal AUDIT-C score, but the multiple GWS findings unique to AUD argue against that as an explanation for the non-overlapping GWS findings for the two traits.