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

  1. Barbara A. Gower1,
  2. José R. Fernández12,
  3. T. Mark Beasley2,
  4. Mark D. Shriver3 and
  5. Michael I. Goran4
  1. 1Department of Nutrition Sciences and Clinical Nutrition Research Center, the University of Alabama at Birmingham, Birmingham, Alabama
  2. 2Department of Biostatistics, Section of Statistical Genetics, the University of Alabama at Birmingham, Birmingham, Alabama
  3. 3Department of Anthropology, Pennsylvania State University, State College, Pennsylvania
  4. 4Departments of Preventive Medicine and Physiology and Biophysics, University of Southern California, Los Angeles, California

    Abstract

    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 (SI), fasting insulin, and the acute insulin response to glucose (AIRg) 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 SI, fasting insulin, and AIRg 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 SI (P < 0.001) and fasting insulin (P < 0.01), with individuals having greater African ADM having a lower SI and a higher fasting insulin concentration. Both ADM (P < 0.001) and SES (P < 0.05) were independently related to AIRg; children with greater African ADM or lower SES had a higher AIRg, even after adjusting for SI. These observations suggest that use of ADM can replace assignment of individuals to categorical racial groups; that lower SI and higher fasting insulin among African Americans compared with European Americans may have a genetic basis; and that higher AIRg among African Americans may be due to both genetic factors and to environmental factors that remain to be identified.

    Footnotes

    • Address correspondence and reprint requests to Barbara A. Gower, Department of Nutrition Sciences, University of Alabama at Birmingham, 423 Webb Bldg., 1675 University Blvd., Birmingham, AL 35294-3360. E-mail: bgower{at}uab.edu.

      Received for publication 9 July 2001 and accepted in revised form 2 December 2002.

      ADM, genetic admixture; AIRg, acute insulin response to glucose; SES, socioeconomic status; SI, insulin sensitivity.

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