Data from: Admixture mapping in two Mexican samples identifies significant associations of locus ancestry with triglyceride levels in the BUD13/ZNF259/APOA5 region and fine mapping points to rs964184 as the main driver of the association signal

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.

我们针对墨西哥城的两组样本开展了脂质性状的混血定位分析。美洲原住民血统与11号染色体大范围区域内的甘油三酯水平显著相关，该区域覆盖BUD13、ZNF259及APOA5基因。我们利用高密度全基因组数据对该区域开展精细定位分析后发现，rs964184是唯一纳入99%单核苷酸多态性（Single Nucleotide Polymorphisms, SNPs）可信集的标记位点，这为rs964184是该区域内的致病变异提供了强有力的证据支持。与甘油三酯水平升高相关的等位基因（rs964184-G）在墨西哥籍美洲原住民人群中的出现频率较欧洲人群高出30%~40%。目前针对该变异的相关研究证据表明，其可能通过三种潜在机制发挥调控作用：1）改变增强子活性；2）顺式和/或反式调控多个基因的表达；3）改变APOA5基因启动子区域的甲基化模式。