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Population Structure of Hispanics in the United States: The Multi-Ethnic Study of Atherosclerosis

Author

Listed:
  • Ani Manichaikul
  • Walter Palmas
  • Carlos J Rodriguez
  • Carmen A Peralta
  • Jasmin Divers
  • Xiuqing Guo
  • Wei-Min Chen
  • Quenna Wong
  • Kayleen Williams
  • Kathleen F Kerr
  • Kent D Taylor
  • Michael Y Tsai
  • Mark O Goodarzi
  • Michèle M Sale
  • Ana V Diez-Roux
  • Stephen S Rich
  • Jerome I Rotter
  • Josyf C Mychaleckyj

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. Author Summary: Using genotype data from about 60,000 distinct genetic markers, we examined population structure in 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 comparing genetic ancestry of MESA Hispanic participants to reference samples representing worldwide diversity, we show major differences in ancestry of MESA Hispanics reflecting their Caucasian, African, and Native American origins, with finer differences corresponding to North-South geographic origins that separate MESA Mexican versus Central/South American samples. Based on our analysis, we define four subgroups of the MESA Hispanic cohort that show close agreement with the following self-identified regions of origin: Dominican/Cuban, Mexican, Central/South American, and Puerto Rican. We examine association of triglycerides with selected genetic markers, and we further demonstrate the importance of considering differences in genetic ancestry (or factors associated with genetic ancestry) when performing genetic studies of the United States Hispanic population.

Suggested Citation

  • Ani Manichaikul & Walter Palmas & Carlos J Rodriguez & Carmen A Peralta & Jasmin Divers & Xiuqing Guo & Wei-Min Chen & Quenna Wong & Kayleen Williams & Kathleen F Kerr & Kent D Taylor & Michael Y Tsai, 2012. "Population Structure of Hispanics in the United States: The Multi-Ethnic Study of Atherosclerosis," PLOS Genetics, Public Library of Science, vol. 8(4), pages 1-14, April.
  • Handle: RePEc:plo:pgen00:1002640
    DOI: 10.1371/journal.pgen.1002640
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    References listed on IDEAS

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    1. Nick Patterson & Alkes L Price & David Reich, 2006. "Population Structure and Eigenanalysis," PLOS Genetics, Public Library of Science, vol. 2(12), pages 1-20, December.
    2. Zhaoming Wang & Allan Hildesheim & Sophia S Wang & Rolando Herrero & Paula Gonzalez & Laurie Burdette & Amy Hutchinson & Gilles Thomas & Stephen J Chanock & Kai Yu, 2010. "Genetic Admixture and Population Substructure in Guanacaste Costa Rica," PLOS ONE, Public Library of Science, vol. 5(10), pages 1-10, October.
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