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Using Genetic Admixture to Explain Racial Differences in Insulin-Related Phenotypes

¹ Department of Nutrition Sciences and Clinical Nutrition Research Center, the University of Alabama at Birmingham, Birmingham, Alabama
² Department of Biostatistics, Section of Statistical Genetics, the University of Alabama at Birmingham, Birmingham, Alabama
³ Department of Anthropology, Pennsylvania State University, State College, Pennsylvania
⁴ Departments of Preventive Medicine and Physiology and Biophysics, University of Southern California, Los Angeles, California

Documented differences in measures of insulin secretion and action between African Americans and European Americans may be due to either genetic or environmental factors. This study used genetic admixture (ADM), determined from 20 ancestry informative markers, and a questionnaire designed to assess socioeconomic status (SES) to examine potential genetic and environmental contributions to minimal model–derived measures of insulin sensitivity (S_I), fasting insulin, and the acute insulin response to glucose (AIR_g) in 125 children residing in Birmingham, Alabama. The study was longitudinal in design and yielded multiple outcome measures on each subject. Mixed models analysis was used to determine if ADM and SES were independently related to S_I, fasting insulin, and AIR_g after adjusting for confounding factors (pubertal status, adiposity, age) and for repeated testing of individuals. In this cohort, African ADM ranged from 0% (individuals with no markers reflecting African ancestry) to 100% (individuals with all 20 markers reflecting African ancestry). Results indicated that ADM was independently related to S_I (P < 0.001) and fasting insulin (P < 0.01), with individuals having greater African ADM having a lower S_I and a higher fasting insulin concentration. Both ADM (P < 0.001) and SES (P < 0.05) were independently related to AIR_g; children with greater African ADM or lower SES had a higher AIR_g, even after adjusting for S_I. These observations suggest that use of ADM can replace assignment of individuals to categorical racial groups; that lower S_I and higher fasting insulin among African Americans compared with European Americans may have a genetic basis; and that higher AIR_g among African Americans may be due to both genetic factors and to environmental factors that remain to be identified.

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