Colloquium paper: genome-wide patterns of population structure and admixture among Hispanic/Latino populations

Abstract

Hispanic/Latino populations possess a complex genetic structure that reflects recent admixture among and potentially ancient substructure within Native American, European, and West African source populations. Here, we quantify genome-wide patterns of SNP and haplotype variation among 100 individuals with ancestry from Ecuador, Colombia, Puerto Rico, and the Dominican Republic genotyped on the Illumina 610-Quad arrays and 112 Mexicans genotyped on Affymetrix 500K platform. Intersecting these data with previously collected high-density SNP data from 4,305 individuals, we use principal component analysis and clustering methods FRAPPE and STRUCTURE to investigate genome-wide patterns of African, European, and Native American population structure within and among Hispanic/Latino populations. Comparing autosomal, X and Y chromosome, and mtDNA variation, we find evidence of a significant sex bias in admixture proportions consistent with disproportionate contribution of European male and Native American female ancestry to present-day populations. We also find that patterns of linkage-disequilibria in admixed Hispanic/Latino populations are largely affected by the admixture dynamics of the populations, with faster decay of LD in populations of higher African ancestry. Finally, using the locus-specific ancestry inference method LAMP, we reconstruct fine-scale chromosomal patterns of admixture. We document moderate power to differentiate among potential subcontinental source populations within the Native American, European, and African segments of the admixed Hispanic/Latino genomes. Our results suggest future genome-wide association scans in Hispanic/Latino populations may require correction for local genomic ancestry at a subcontinental scale when associating differences in the genome with disease risk, progression, and drug efficacy, as well as for admixture mapping.

Fig. 1.

Frappe clustering illustrating the admixed ancestry of Hispanic/Latinos shown for K = 3 and K = 7. Individuals are shown as vertical bars colored in proportion to their estimated ancestry within each cluster. Native American populations are listed in order geographically, from North to South.

Fig. 2.

Principal component analysis results of the Hispanic/Latino individuals with Europeans, Africans, and Native Americans. PC 1 vs. PC 2 scatter plots based on autosomal markers (Upper Left) and based on X chromosome markers (Upper Right). Ellipses are fitted to the PCA results on the autosomes (Lower Left) and to results from the X chromosome markers (Lower Right).

Fig. 3.

Genome-wide and locus specific ancestry estimates for Mexicans, Ecuadorians, Colombians, Puerto Ricans, and Dominicans. Shown for K = 3, clustering of the Hispanic/Latino individuals on the autosomes (Top) and on the X chromosome (Bottom). Individuals are shown as vertical bars colored in proportion to their estimated ancestry within each cluster. Local ancestry at each locus is shown for each individual on chromosome 1 (Middle). The X chromosome shows greater Native American ancestry (blue) and greater variability in African ancestry (green), with reduced European ancestry (red).

Fig. 4.

Linkage disequilibrium, genotype r² estimated by PLINK, by population as a function of physical distance (Mb). (Left) Native American, European, and African populations. (Right) Hispanic/Latino populations. Scale is the same.

Fig. 5.

Boxplots comparing autosomal vs. X chromosome ancestry proportions by population, shown for European ancestry (Left), Native American ancestry (Center), and African ancestry (Right). Filled boxes correspond to autosomal ancestry estimates; open boxes show X chromosome ancestry estimates. Median (solid line), first and third quartiles (box) and the minimum/maximum values, or to the smallest value within 1.5 times the IQR from the first quartile (whiskers). For each paired comparison of X chromosomes and autosomes, median Native American ancestries are consistently higher on the X chromosome in all Hispanic/Latino populations sampled, and European ancestries are lower across all populations.

Fig. 6.

Comparison of mtDNA and Y chromosome haplotypes. Each individual is represented by a point within the triangle that represents the autosomal ancestry proportions. The most probable continental location for each individual’s haplotype is designated by the color of the point. The Y chromosome contains a disproportionate number of European haplotypes, whereas the mtDNA has a high proportion of Native American, slightly more African haplotypes and fewer European haplotypes, consistent with a sex bias toward a great European male and Native American/African female ancestry in the Hispanic/Latinos.