Racial/Ethnic Differences in Association of Fasting Glucose–Associated Genomic Loci With Fasting Glucose, HOMA-B, and Impaired Fasting Glucose in the U.S. Adult Population
- Quanhe Yang, PHD1,
- Tiebin Liu, MSPH1,
- Peter Shrader, MS2,
- Ajay Yesupriya, MPH1,
- Man-huei Chang, MPH1,
- Nicole F. Dowling, PHD1,
- Renée M. Ned, MMSC, PHD1,
- Josée Dupuis, PHD3,
- Jose C. Florez, MD, PHD4,
- Muin J. Khoury, MD, PHD1,
- James B. Meigs, MD, MPH5 and
- the MAGIC Investigators*
- 1Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia;
- 2General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts;
- 3Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts;
- 4Center for Human Genetic Research and Diadetes Research Center (Diabetes Unit), Massachusetts General Hospital, Program in Medical and Population Genetics, Broad Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts;
- 5General Medicine Division, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts.
- Corresponding author: Quanhe Yang, .
OBJECTIVE To estimate allele frequencies and the marginal and combined effects of novel fasting glucose (FG)-associated single nucleotide polymorphisms (SNPs) on FG levels and on risk of impaired FG (IFG) among non-Hispanic white, non-Hispanic black, and Mexican Americans.
RESEARCH DESIGN AND METHODS DNA samples from 3,024 adult fasting participants in the National Health and Nutrition Examination Survey (NHANES) III (1991–1994) were genotyped for 16 novel FG-associated SNPs in multiple genes. We determined the allele frequencies and influence of these SNPs alone and in a weighted genetic risk score on FG, homeostasis model assessment of β-cell function (HOMA-B), and IFG by race/ethnicity, while adjusting for age and sex.
RESULTS All allele frequencies varied significantly by race/ethnicity. A weighted genetic risk score, based on 16 SNPs, was associated with a 0.022 mmol/l (95% CI 0.009–0.035), 0.036 mmol/l (0.019–0.052), and 0.033 mmol/l (0.020–0.046) increase in FG levels per risk allele among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans, respectively. Adjusted odds ratios for IFG were 1.78 for non-Hispanic whites (95% CI 1.00–3.17), 2.40 for non-Hispanic blacks (1.07–5.37), and 2.39 for Mexican Americans (1.37–4.14) when we compared the highest with the lowest quintiles of genetic risk score (P = 0.365 for testing heterogeneity of effect across race/ethnicity).
CONCLUSIONS We conclude that allele frequencies of 16 novel FG-associated SNPs vary significantly by race/ethnicity, but the influence of these SNPs on FG levels, HOMA-B, and IFG were generally consistent across all racial/ethnic groups.
↵*The MAGIC Investigators are listed in the online appendix, available at http://care.diabetesjournals.org/cgi/content/full/dc10-0898/DC1.
The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Received May 10, 2010.
- Accepted August 17, 2010.
- © 2010 by the American Diabetes Association.
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