Evidence for Association Between SH2B1 Gene Variants and Glycated Hemoglobin in Nondiabetic European American Young Adults

The Add Health Study

Published in: Annals of Human Genetics, v. 80, no. 5, Sep. 2016, p. 294-305

Posted on RAND.org on September 29, 2016

by Leslie A. Lange, Mariaelisa Graff, Ethan M. Lange, Kristin L. Young, Andrea Richardson, Karen L. Mohlke, Kari E. North, Kathleen Harris, Penny Gordon-Larsen

Glycated hemoglobin (HbA1c) is used to classify glycaemia and type 2 diabetes (T2D). Body mass index (BMI) is a predictor of HbA1c levels and T2D. We tested 43 established BMI and obesity loci for association with HbA1c in a nationally representative multiethnic sample of young adults from the National Longitudinal Study of Adolescent to Adult Health [Add Health: age 24-34 years; n = 5641 European Americans (EA); 1740 African Americans (AA); 1444 Hispanic Americans (HA)] without T2D, using two levels of covariate adjustment (Model 1: age, sex, smoking, and geographic region; Model 2: Model 1 covariates plus BMI). Bonferroni adjustment was made for 43 SNPs and we considered P < 0.0011 statistically significant. Means (SD) for HbA1c were 5.4% (0.3) in EA, 5.7% (0.4) in AA, and 5.5% (0.3) in HA. We observed significant evidence for association with HbA1c for two variants near SH2B1 in EA (rs4788102, P = 2.2 × 10−4; rs7359397, P = 9.8 × 10−4) for Model 1. Both results were attenuated after adjustment for BMI (rs4788102, P = 1.7 × 10−3; rs7359397, P = 4.6 × 10−3). No variant reached Bonferroni-corrected significance in AA or HA. These results suggest that SH2B1 polymorphisms are associated with HbA1c, largely independent of BMI, in EA young adults.

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