The Relationship between Native American Ancestry, Body Mass Index and Diabetes Risk among Mexican-Americans

<div><p>Higher body mass index (BMI) is a well-established risk factor for type 2 diabetes, and rates of obesity and type 2 diabetes are substantially higher among Mexican-Americans relative to non-Hispanic European Americans. Mexican-Americans are genetically diverse, with a highly variable distribution of Native American, European, and African ancestries. Here, we evaluate the role of Native American ancestry on BMI and diabetes risk in a well-defined Mexican-American population. Participants were randomly selected among individuals residing in the Houston area who are enrolled in the Mexican-American Cohort study. Using a custom Illumina GoldenGate Panel, we genotyped DNA from 4,662 cohort participants for 87 Ancestry-Informative Markers. On average, the participants were of 50.2% Native American ancestry, 42.7% European ancestry and 7.1% African ancestry. Using multivariate linear regression, we found BMI and Native American ancestry were inversely correlated; individuals with <20% Native American ancestry were 2.5 times more likely to be severely obese compared to those with >80% Native American ancestry. Furthermore, we demonstrated an interaction between BMI and Native American ancestry in diabetes risk among women; Native American ancestry was a strong risk factor for diabetes only among overweight and obese women (OR = 1.190 for each 10% increase in Native American ancestry). This study offers new insight into the complex relationship between obesity, genetic ancestry, and their respective effects on diabetes risk. Findings from this study may improve the diabetes risk prediction among Mexican-American individuals thereby facilitating targeted prevention strategies.</p></div

Association between genetic ancestry and BMI.

<p>*Shown in the parentheses are the 95% confidence interval of the regression coefficient</p><p>Association between genetic ancestry and BMI.</p

Genetic ancestries of 4,659 participants in the Mexican-American Cohort.

<p>Each column represents one individual. The lengths of lines with different colors in each column represent the proportion of genetic ancestry for this individual. Green: European; Blue: Native American; Red: African.</p

Genetic ancestry by gender.

<p>*p-values are calculated with Wilcoxon rank sum test.</p><p>Genetic ancestry by gender.</p

Demographic characteristics of participants.

<p>* p-values are calculated with Wilcoxon rank sum test for age and BMI, and with Fisher exact test otherwise.</p><p>Demographic characteristics of participants.</p

A comparison of phenotypic variation explained by different numbers of SNPs in close relatives.

<p>Variation of height explained by 10%, 30%, 50%, 80% and 100% of the nearly one million autosomal SNPs. Results are shown for two samples of related (z1> = 0.3, blue line and z1> = 0.4, red line) individuals.</p

Cross-trait associations for novel loci from Stage1 + Stage 2 in participants of African ancestry.

1<p>effect allele/other allele.</p>2<p>effect size based on Stage 1 and Stage 2 combined sample.</p