Abstract
BackgroundPopulation 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.ResultsWe 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.ConclusionThese 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.
Highlights
Population structure and admixture have strong confounding effects on genetic association studies
We focus on the modeling results of K = 4 for which the second largest likelihood [lnPr(X|K = 4) = -116312.20] where the average Los Angeles Latino Eye Study (LALES) Latino admixture is partitioned as 45.2 - 54.3% Native American, 32.1 - 40.1% European, 9.7 - 11.5% Asian, and 4.0 - 5.2% African-American (Tables 2 and 3)
Depending on the details of which SNPs were incorporated in our analysis and, correspondingly, which African populations were used as a reference, the LALES Latinos were estimated to inherit in the region of 50% NA and 40% EU ancestry
Summary
Population structure and admixture have strong confounding effects on genetic association studies. The CY3A4-V gene variant and prostate cancer are reported to be substantially less common among European American than African American (AA) men; Kittles et al studied 688 AAs and found that a strongly significant association at CYP3A4-V for prostate cancer became a non-significant signal after including ten ancestry informative markers (AIMs) [19]. Several discrepancies in both disease prevalence rates and genetic susceptibility loci have been confirmed in Latino studies.
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