title: Evidence for Association between SH2B1 Gene Variants and Glycated Hemoglobin in Nondiabetic European American Young Adults: The Add Health Study.
abstract: 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.
authors.affiliation: Department of Genetics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Carolina Center for Genome Sciences, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Carolina Population Center, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Mariaelisa
authors.initials: M
authors.lastname: Graff
authors.affiliation: Department of Genetics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Carolina Center for Genome Sciences, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Deptartment of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Carolina Population Center, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Young
authors.affiliation: Carolina Population Center, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Department of Sociology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Richardson
authors.affiliation: Department of Genetics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Carolina Center for Genome Sciences, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mohlke
authors.affiliation: Carolina Center for Genome Sciences, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.affiliation: Carolina Population Center, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Harris
authors.affiliation: Carolina Population Center, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.|Department of Sociology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Penny
authors.initials: P
authors.lastname: Gordon-Larsen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D014481:United States; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006442:Glycated Hemoglobin; C518910:SH2B1 protein, human; C517652:hemoglobin A1c protein, human
keywords: HBA1c; Obesity; diabetes