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

PLoS One. 2017 Feb 28;12(2):e0172880. doi: 10.1371/journal.pone.0172880. eCollection 2017.

Abstract

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.

MeSH terms

  • Adult
  • Alleles
  • Apolipoprotein A-V / genetics*
  • Carrier Proteins / genetics*
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Membrane Transport Proteins
  • Mexican Americans
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • RNA-Binding Proteins / genetics*
  • Triglycerides / blood*
  • White People

Substances

  • APOA5 protein, human
  • Apolipoprotein A-V
  • BUD13 homolog protein, human
  • Carrier Proteins
  • Membrane Transport Proteins
  • RNA-Binding Proteins
  • Triglycerides
  • ZPR1 protein, human