Parra, Esteban J.;
Mazurek, Andrew;
Gignoux, Christopher R.;
Sockell, Alexandra;
Agostino, Michael;
Morris, Andrew P.;
Petty, Lauren E.;
Hanis, Craig L.;
Cox, Nancy J.;
Valladares-Salgado, Adan;
Below, Jennifer E.;
Cruz, Miguel
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2018-02-15
We carried out an admixture mapping study of lipid traits in two samples from Mexico City. Native American locus ancestry was significantly associated with triglyceride levels in a broad region of chromosome 11 overlapping the BUD13, ZNF259 and APOA5 genes. In our fine-mapping analysis of this region using dense genome-wide data, rs964184 is the only marker included in the 99% credible set of SNPs, providing strong support for rs964184 as the causal variant within this region. The frequency of the allele associated with increased triglyceride concentrations (rs964184-G) is between 30-40% higher in Native American populations from Mexico than in European populations. The evidence currently available for this variant indicates that it may be exerting its effect through three potential mechanisms: 1) modification of enhancer activity, 2) regulation of the expression of several genes in cis and/or trans, or 3) modification of the methylation patterns of the promoter of the APOA5 gene.