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

• Published in: PLoS genetics Vol. 8; no. 4; p. e1002640
• Main Authors: Manichaikul, Ani, Palmas, Walter, Rodriguez, Carlos J., Peralta, Carmen A., Divers, Jasmin, Guo, Xiuqing, Chen, Wei-Min, Wong, Quenna, Williams, Kayleen, Kerr, Kathleen F., Taylor, Kent D., Tsai, Michael Y., Goodarzi, Mark O., Sale, Michèle M., Diez-Roux, Ana V., Rich, Stephen S., Rotter, Jerome I., Mychaleckyj, Josyf C.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2012; Public Library of Science (PLoS)
• Subjects: Age; Atherosclerosis; Atherosclerosis - epidemiology; Atherosclerosis - genetics; Biology; Black or African American; Black People - genetics; Cardiovascular disease; Cluster Analysis; Demographic aspects; Gender; Genealogy; Genetic aspects; Genetic Association Studies; Genetics; Genomes; HapMap Project; Health aspects; Hispanic Americans; Hispanic or Latino - genetics; Humans; Indians, North American - genetics; Intracellular Signaling Peptides and Proteins - genetics; Lipoprotein Lipase - genetics; Multiculturalism & pluralism; Physiological aspects; Polymorphism, Single Nucleotide - genetics; Population; Population genetics; Population Groups - genetics; Principal components analysis; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - genetics; Studies; Triglycerides; Triglycerides - blood; Triglycerides - genetics; United States; White People - genetics; United States; South America; Cuba; Central America; Puerto Rico; United States > US; Dominican Republic; Mexico
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1002640

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.