Population structure of Hispanics in the United States: the multi-ethnic study of atherosclerosis

PLoS Genet. 2012;8(4):e1002640. doi: 10.1371/journal.pgen.1002640. Epub 2012 Apr 12.

Abstract

Using ~60,000 SNPs selected for minimal linkage disequilibrium, we perform population structure analysis of 1,374 unrelated Hispanic individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with self-identification corresponding to Central America (n = 93), Cuba (n = 50), the Dominican Republic (n = 203), Mexico (n = 708), Puerto Rico (n = 192), and South America (n = 111). By projection of principal components (PCs) of ancestry to samples from the HapMap phase III and the Human Genome Diversity Panel (HGDP), we show the first two PCs quantify the Caucasian, African, and Native American origins, while the third and fourth PCs bring out an axis that aligns with known South-to-North geographic location of HGDP Native American samples and further separates MESA Mexican versus Central/South American samples along the same axis. Using k-means clustering computed from the first four PCs, we define four subgroups of the MESA Hispanic cohort that show close agreement with self-identification, labeling the clusters as primarily Dominican/Cuban, Mexican, Central/South American, and Puerto Rican. To demonstrate our recommendations for genetic analysis in the MESA Hispanic cohort, we present pooled and stratified association analysis of triglycerides for selected SNPs in the LPL and TRIB1 gene regions, previously reported in GWAS of triglycerides in Caucasians but as yet unconfirmed in Hispanic populations. We report statistically significant evidence for genetic association in both genes, and we further demonstrate the importance of considering population substructure and genetic heterogeneity in genetic association studies performed in the United States Hispanic population.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • African Continental Ancestry Group / genetics
  • Atherosclerosis* / epidemiology
  • Atherosclerosis* / genetics
  • Cluster Analysis
  • European Continental Ancestry Group / genetics
  • Genetic Association Studies*
  • HapMap Project
  • Hispanic Americans / genetics*
  • Humans
  • Indians, North American / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lipoprotein Lipase / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Population Groups / genetics
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Triglycerides* / blood
  • Triglycerides* / genetics
  • United States

Substances

  • Intracellular Signaling Peptides and Proteins
  • TRIB1 protein, human
  • Triglycerides
  • Protein-Serine-Threonine Kinases
  • LPL protein, human
  • Lipoprotein Lipase