Differences in albuminuria between Hispanics and whites: an evaluation by genetic ancestry and country of origin: the multi-ethnic study of atherosclerosis.

BACKGROUND: Reports show higher prevalence of albuminuria among Hispanics compared with whites. Differences by country of origin or genetic background are unknown. METHODS AND RESULTS: In Multi-Ethnic Study of Atherosclerosis, we studied the associations of both genetic ancestry and country of origin with albumin to creatinine ratio among 1417 Hispanic versus white participants using multivariable linear regression and back transforming beta coefficients into relative difference (%RD, 95% CI). Percentage European, Native American, and African ancestry components for Hispanics were estimated using genetic admixture analysis. The proportions of European, Native American, and African genetic ancestry differed significantly by country of origin (P<0.0001); Mexican/Central Americans had the highest Native American (41+/-13%), Puerto Ricans had the highest European (61+/-15%), and Dominicans had the highest African (39+/-21%) ancestry. Hispanic ethnicity was associated with higher albumin/creatinine ratio compared with whites, but the association varied with the country of origin (adjusted P interaction=0.04). Mexican/Central Americans and Dominicans had higher albumin/creatinine ratio compared with whites after adjustment (RD 19%, 2% to 40% and RD 27%, 1% to 61%), but not Puerto Ricans (RD 8%, -12% to 34%). Higher Native American ancestry was associated with higher albuminuria after age and sex adjustment among all Hispanics (RD 11%, 1% to 21%) but was attenuated after further adjustment. Higher European ancestry was independently associated with lower albumin/creatinine ratio among Puerto Ricans (-21%, -34% to -6%) but not among Mexican/Central Americans and Dominicans. CONCLUSIONS: Hispanics are a heterogeneous group with varying genetic ancestry. Risks of albuminuria differ across the country of origin groups. These differences may be due, in part, to differences in genetic ancestral components.

A genomewide single-nucleotide-polymorphism panel for Mexican American admixture mapping.

For admixture mapping studies in Mexican Americans (MAM), we define a genomewide single-nucleotide-polymorphism (SNP) panel that can distinguish between chromosomal segments of Amerindian (AMI) or European (EUR) ancestry. These studies used genotypes for >400,000 SNPs, defined in EUR and both Pima and Mayan AMI, to define a set of ancestry-informative markers (AIMs). The use of two AMI populations was necessary to remove a subset of SNPs that distinguished genotypes of only one AMI subgroup from EUR genotypes. The AIMs set contained 8,144 SNPs separated by a minimum of 50 kb with only three intermarker intervals >1 Mb and had EUR/AMI FST values >0.30 (mean FST = 0.48) and Mayan/Pima FST values <0.05 (mean FST < 0.01). Analysis of a subset of these SNP AIMs suggested that this panel may also distinguish ancestry between EUR and other disparate AMI groups, including Quechuan from South America. We show, using realistic simulation parameters that are based on our analyses of MAM genotyping results, that this panel of SNP AIMs provides good power for detecting disease-associated chromosomal segments for genes with modest ethnicity risk ratios. A reduced set of 5,287 SNP AIMs captured almost the same admixture mapping information, but smaller SNP sets showed substantial drop-off in admixture mapping information and power. The results will enable studies of type 2 diabetes, rheumatoid arthritis, and other diseases among which epidemiological studies suggest differences in the distribution of ancestry-associated susceptibility.

Argentine population genetic structure: large variance in Amerindian contribution.

Argentine population genetic structure was examined using a set of 78 ancestry informative markers (AIMs) to assess the contributions of European, Amerindian, and African ancestry in 94 individuals members of this population. Using the Bayesian clustering algorithm STRUCTURE, the mean European contribution was 78%, the Amerindian contribution was 19.4%, and the African contribution was 2.5%. Similar results were found using weighted least mean square method: European, 80.2%; Amerindian, 18.1%; and African, 1.7%. Consistent with previous studies the current results showed very few individuals (four of 94) with greater than 10% African admixture. Notably, when individual admixture was examined, the Amerindian and European admixture showed a very large variance and individual Amerindian contribution ranged from 1.5 to 84.5% in the 94 individual Argentine subjects. These results indicate that admixture must be considered when clinical epidemiology or case control genetic analyses are studied in this population. Moreover, the current study provides a set of informative SNPs that can be used to ascertain or control for this potentially hidden stratification. In addition, the large variance in admixture proportions in individual Argentine subjects shown by this study suggests that this population is appropriate for future admixture mapping studies.

Mexican American ancestry-informative markers: examination of population structure and marker characteristics in European Americans, Mexican Americans, Amerindians and Asians.

Markers with large differences in allele frequencies between ethnicities provide ancestry information that can be applied to genetic studies. We identified over 100 biallelic ancestry informative markers (AIMs) with large allele frequency differences between European Americans (EA) and Pima Amerindians from laboratory and database screens. For 35 of these markers, Mayan, Yavapai and Quechuan Amerindians were genotyped and compared with EA and Pima allele frequencies. Markers with large allele frequency differences between EA and one Amerindian tribe showed only small differences between the Amerindian tribes. Examination of structure in individuals demonstrated a clear separation of subjects of European from those of Amerindian ancestry, and similarity between individuals from disparate Amerindian populations. The AIMs demonstrated the variation in ancestral composition of individual Mexican Americans, providing evidence of applicability in admixture mapping and in controlling for structure in association tests. In addition, a high percentage of single-nucleotide polymorphisms (SNPs) selected on the basis of large frequency differences between EA and Asian populations had large allele frequency differences between EA and Amerindians, suggesting an efficient method for greatly expanding AIMs for use in admixture mapping/structure analysis in Mexican Americans. Together, these data provide additional support for the practical application of admixture mapping in the Mexican American population.