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Chunk #20 — DISCUSSION

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Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders.
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The only other locus to reach significance was rs7644567 on chromosome 3, primarily driven by AA cohorts. The locus failed to replicate in two small, independent AA samples, and in the only European cohort with even a modest allele frequency (FINRISK) the effect was in the opposite direction. There have also been discussions about whether the standard GWAS significance threshold should be applied to the more genetically diverse African-ancestry cohorts22,23 and the possibility of confounding from non-linear relationships between the phenotype and ancestry-informative markers like rs7644567 in admixed samples24, all of which increase our skepticism regarding this finding. There is, therefore, insufficient evidence at this time to conclude that rs7644567 is associated with alcohol dependence. Analyses of much larger samples of African ancestry will be needed to resolve this.