Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians.

Published

Journal Article

Glycated hemoglobin A1c (HbA1c) is used as a measure of glycemic control and also as a diagnostic criterion for diabetes. To discover novel loci harboring common variants associated with HbA1c in East Asians, we conducted a meta-analysis of 13 genome-wide association studies (GWAS; N = 21,026). We replicated our findings in three additional studies comprising 11,576 individuals of East Asian ancestry. Ten variants showed associations that reached genome-wide significance in the discovery data set, of which nine (four novel variants at TMEM79 [P value = 1.3 × 10(-23)], HBS1L/MYB [8.5 × 10(-15)], MYO9B [9.0 × 10(-12)], and CYBA [1.1 × 10(-8)] as well as five variants at loci that had been previously identified [CDKAL1, G6PC2/ABCB11, GCK, ANK1, and FN3KI]) showed consistent evidence of association in replication data sets. These variants explained 1.76% of the variance in HbA1c. Several of these variants (TMEM79, HBS1L/MYB, CYBA, MYO9B, ANK1, and FN3K) showed no association with either blood glucose or type 2 diabetes. Among individuals with nondiabetic levels of fasting glucose (<7.0 mmol/L) but elevated HbA1c (≥6.5%), 36.1% had HbA1c <6.5% after adjustment for these six variants. Our East Asian GWAS meta-analysis has identified novel variants associated with HbA1c as well as demonstrated that the effects of known variants are largely transferable across ethnic groups. Variants affecting erythrocyte parameters rather than glucose metabolism may be relevant to the use of HbA1c for diagnosing diabetes in these populations.

Full Text

Duke Authors

Cited Authors

  • Chen, P; Takeuchi, F; Lee, J-Y; Li, H; Wu, J-Y; Liang, J; Long, J; Tabara, Y; Goodarzi, MO; Pereira, MA; Kim, YJ; Go, MJ; Stram, DO; Vithana, E; Khor, C-C; Liu, J; Liao, J; Ye, X; Wang, Y; Lu, L; Young, TL; Lee, J; Thai, AC; Cheng, C-Y; van Dam, RM; Friedlander, Y; Heng, C-K; Koh, W-P; Chen, C-H; Chang, L-C; Pan, W-H; Qi, Q; Isono, M; Zheng, W; Cai, Q; Gao, Y; Yamamoto, K; Ohnaka, K; Takayanagi, R; Kita, Y; Ueshima, H; Hsiung, CA; Cui, J; Sheu, WH-H; Rotter, JI; Chen, Y-DI; Hsu, C; Okada, Y; Kubo, M; Takahashi, A; Tanaka, T; van Rooij, FJA; Ganesh, SK; Huang, J; Huang, T; Yuan, J; Hwang, J-Y; CHARGE Hematology Working Group, ; Gross, MD; Assimes, TL; Miki, T; Shu, X-O; Qi, L; Chen, Y-T; Lin, X; Aung, T; Wong, T-Y; Teo, Y-Y; Kim, B-J; Kato, N; Tai, E-S

Published Date

  • July 2014

Published In

Volume / Issue

  • 63 / 7

Start / End Page

  • 2551 - 2562

PubMed ID

  • 24647736

Pubmed Central ID

  • 24647736

Electronic International Standard Serial Number (EISSN)

  • 1939-327X

Digital Object Identifier (DOI)

  • 10.2337/db13-1815

Language

  • eng

Conference Location

  • United States