Abstract
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.
Highlights
The Mexican-American population is a genetically diverse ethnic group with varying proportions of Native American, European and African ancestry
When Body Mass Index (BMI) was not included as a covariate, we found that Native American ancestry was a significant risk factor for diabetes, with an OR of 1.067 for a 10% increase in Native American ancestry (p = 0.037; Table 4), which is consistent with previous estimate within American Indian and Alaska Native adults [25]
We identified an inverse association between BMI and Native American ancestry in the Mexican American population in Houston, Texas
Summary
The Mexican-American population is a genetically diverse ethnic group with varying proportions of Native American, European and African ancestry. A second study of 846 Native American participants recruited from 8 Native American reservations reported a significant positive correlation (p = 1.46e-4) [12], In contrast, a study involving 1,506 Mexican Americans from Starr County, Texas found a negative correlation between Native American ancestry and BMI (p = 0.011)[13] Each of these studies used genetic markers to estimate individual ancestry and each controlled for socio-economic status. In a sample of Latino populations containing 662 type 2 diabetes cases and 269 controls from central Mexico and Colombia, researchers [6] estimated the amount of European genetic ancestry by genotyping 67 ancestry informative markers (AIM) among participants They found that non-European ancestry was positively correlated with type 2 diabetes risk (odds ratio of 16.7 and 3.8 for a 100% increase in non-European ancestry in Mexicans and Colombians, respectively). 0.163 1.41E-06 7.81E-07 2.43E-06 2.06E-01 1.38E-01 each individual using ADMIXTURE [22] and evaluate the relationship between genetic ancestry, BMI, and diabetes risk in this population
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