Variation in genetic admixture and population structure among Latinos: the Los Angeles Latino eye study (LALES)

Abstract

Background: Population structure and admixture have strong confounding effects on genetic association studies. Discordant frequencies for age-related macular degeneration (AMD) risk alleles and for AMD incidence and prevalence rates are reported across different ethnic groups. We examined the genomic ancestry characterizing 538 Latinos drawn from the Los Angeles Latino Eye Study [LALES] as part of an ongoing AMD-association study. To help assess the degree of Native American ancestry inherited by Latino populations we sampled 25 Mayans and 5 Mexican Indians collected through Coriell's Institute. Levels of European, Asian, and African descent in Latinos were inferred through the USC Multiethnic Panel (USC MEP), formed from a sample from the Multiethnic Cohort (MEC) study, the Yoruba African samples from HapMap II, the Singapore Chinese Health Study, and a prospective cohort from Shanghai, China. A total of 233 ancestry informative markers were genotyped for 538 LALES Latinos, 30 Native Americans, and 355 USC MEP individuals (African Americans, Japanese, Chinese, European Americans, Latinos, and Native Hawaiians). Sensitivity of ancestry estimates to relative sample size was considered.

Results: We detected strong evidence for recent population admixture in LALES Latinos. Gradients of increasing Native American background and of correspondingly decreasing European ancestry were observed as a function of birth origin from North to South. The strongest excess of homozygosity, a reflection of recent population admixture, was observed in non-US born Latinos that recently populated the US. A set of 42 SNPs especially informative for distinguishing between Native Americans and Europeans were identified.

Conclusion: These findings reflect the historic migration patterns of Native Americans and suggest that while the 'Latino' label is used to categorize the entire population, there exists a strong degree of heterogeneity within that population, and that it will be important to assess this heterogeneity within future association studies on Latino populations. Our study raises awareness of the diversity within "Latinos" and the necessity to assess appropriate risk and treatment management.

Figure 1

Individual ancestry proportions for the LALES, Multiethnic Cohort, and Native American sampled populations. Population Number Code: AA - MEC African Americans; MEC-LAT - MEC Latinos; JP - MEC Japanese (AS); NH - MEC Native Hawaiians; CH-Sh - China Shanghai (AS); CH-Si - China Singapore (AS); CEPH - CEPH (EU); MEC-EU - MEC Europeans (EU); LALES - LALES Latinos; NA - Native American; YRI - Yoruba Africans

Figure 2

Cluster ancestry distribution for the LALES, Multiethnic Panel, and Native American samples. Each individual is positioned proportional to his/her ancestral similarity to each the three reference groups. Individuals placed at a particular corner are completely assigned to the corresponding population, whereas those in the centroid area are equidistant from each of the three group lineages. LALES Latinos - turquoise; MEC Latinos - pink; African - red; Asian - purple; European - yellow; Native Hawaiian - green; Native American - orange.