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
Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON, Canada.
Department of Genetics, Stanford University, Stanford, CA, United States of America.
PLoS One. 2017 Feb 28;12(2):e0172880. doi: 10.1371/journal.pone.0172880. eCollection 2017.
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.
我们对来自墨西哥城的两个样本进行了脂质性状的混合映射研究。在11号染色体上与BUD13、ZNF259和APOA5基因重叠的一个广泛区域中，美洲原住民基因座祖先与甘油三酯水平显著相关。在我们使用密集的全基因组数据对该区域进行的精细映射分析中，rs964184是99%可信的单核苷酸多态性（SNP）集合中唯一包含的标记，为rs964184作为该区域内的因果变异提供了有力支持。与甘油三酯浓度升高相关的等位基因（rs964184 - G）在来自墨西哥的美洲原住民人群中的频率比欧洲人群高30 - 40%。目前关于该变异的现有证据表明，它可能通过三种潜在机制发挥作用：1）增强子活性的改变；2）顺式和/或反式中几个基因表达的调控；3）APOA5基因启动子甲基化模式的改变。
