title: Population structure of Hispanics in the United States: the multi-ethnic study of atherosclerosis.
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.
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America. amanicha@virginia.edu
authors.forename: Ani
authors.initials: A
authors.lastname: Manichaikul
authors.forename: Walter
authors.initials: W
authors.lastname: Palmas
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Rodriguez
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Peralta
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
authors.forename: Quenna
authors.initials: Q
authors.lastname: Wong
authors.forename: Kayleen
authors.initials: K
authors.lastname: Williams
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kerr
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.forename: Michèle M
authors.initials: MM
authors.lastname: Sale
authors.forename: Ana V
authors.initials: AV
authors.lastname: Diez-Roux
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
mesh_terms: D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics; D044383:Black People / Q000235:genetics; D016000:Cluster Analysis; D056726:Genetic Association Studies; D060148:HapMap Project; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044382:Population Groups / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D014280:Triglycerides / Q000097:blood / Q000235:genetics; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C493170:TRIB1 protein, human; D014280:Triglycerides; D017346:Protein Serine-Threonine Kinases; C548261:LPL protein, human; D008071:Lipoprotein Lipase