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KIAA0040 has been implicated in the risk for alcohol dependence based on multiple well‐powered genome‑wide association meta‑analyses. Three independent studies have reported statistically significant associations with alcohol dependence, wherein KIAA0040 was identified as a novel risk locus. In one meta‑analysis involving 1,283 cases (PMID:21703634), the best novel signal (rs6701037) was attributed to KIAA0040, and a subsequent study integrating 12,481 subjects across four cohorts further confirmed this association (PMID:26173551). Additionally, a study published in The American Journal on Addictions provided genome‑wide significant evidence from an independent cohort (PMID:25278008), thereby reinforcing the contribution of KIAA0040 to the polygenic architecture of alcohol dependence.
The genetic findings, though derived from population‐based meta‑analyses rather than classical family segregation studies, support a moderate level of overall clinical validity. Despite the absence of direct functional assays linking KIAA0040 to alcohol dependence, bioinformatics analyses suggest that the gene might be involved in neural regulatory pathways relevant to addiction. There was no report of traditional family-based segregation of variants because the phenotype is complex and multifactorial in nature.
The reported association is based on robust statistical evidence across independent cohorts, and the genetic signal in KIAA0040 has been replicated consistently across studies. The meta‑analytic evidence indicates that although individual effect sizes may be modest, the cumulative data provide a coherent narrative linking the gene to alcohol dependence risk. Moreover, the genetic evidence has reached a level of significance that supports further investigation and potential clinical utility, even if functional validation remains to be fully established.
In summary, while additional studies are warranted to uncover the precise biological mechanisms involved, the current body of genetic data supports the role of KIAA0040 as a contributing risk locus in alcohol dependence. Key to‑take hybrid message: the replicated association in multiple GWAS meta‑analyses enhances the clinical relevance of KIAA0040, informing both diagnostic decisions and future research directions in the context of alcohol dependence.
Gene–Disease AssociationModerateAssociation demonstrated through three independent meta‑analyses involving over 12,000 subjects (PMID:21703634) and replicated in separate cohorts (PMID:26173551; PMID:25278008), though the complex architecture precludes traditional segregation data. Genetic EvidenceModerateMeta‑analysis results from multiple cohorts revealed significant SNP signals in KIAA0040, supporting its role as a risk locus for alcohol dependence, with replicated p‑values across studies. Functional EvidenceLimitedDirect functional studies are lacking; however, bioinformatics analyses suggest a potential involvement in neural regulatory pathways associated with addiction. |