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Chunk #29 — Discussion

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Dissecting ancestry genomic background in substance dependence genome-wide association studies.
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Our analysis on AD GWAS datasets indicated that multiple variants, located in the surrounding regions of genome-wide significant alleles, have effects modifying the associations between significant alleles and AD symptom counts. Most of them showed high allele ΔFs in African or European ancestries and are potentially involved in regulatory mechanisms. Among them, in AAs, rs12639887 showed significant effects both on ADH1B rs1693457 and ADH1C rs6846835 association with AD symptom counts. This variant is located in a PDLIM5 intronic region, approximately 5 Mb downstream with respect to ADH1B and ADH1C. Both VARIANT and rSNPbase defined it as a regulatory SNP. In particular, VARIANT describes it as being located in an H3K36me3 region, whereas rSNPbase designates it as being involved in proximal, distal and RNA binding protein-mediated regulations. Unfortunately, to best of our knowledge, no information is currently available regarding the role of rs12639887 in ADH1B and ADH1C expression or methylation status in brain tissues. However, according to annotation analysis, we can hypothesize that rs12639887 plays a role in determining the differences observed between AAs and EAs in AD GWAS outcomes of