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

Peng Chen, Fumihiko Takeuchi, Jong Young Lee, Huaixing Li, Jer Yuarn Wu, Jun Liang, Jirong Long, Yasuharu Tabara, Mark O. Goodarzi, Mark A. Pereira, Young Jin Kim, Min Jin Go, Daniel O. Stram, Eranga Vithana, Chiea Chuen Khor, Jianjun Liu, Jiemin Liao, Xingwang Ye, Yiqin Wang, Ling LuTerri L. Young, Jeannette Lee, Ah Chuan Thai, Ching Yu Cheng, Rob M. Van Dam, Yechiel Friedlander, Chew Kiat Heng, Woon Puay Koh, Chien Hsiun Chen, Li Ching Chang, Wen Harn Pan, Bin Qi, Masato Isono, Wei Zheng, Qiuyin Cai, Yutang Gao, Ken Yamamoto, Keizo Ohnaka, Ryoichi Takayanagi, Yoshikuni Kita, Hirotsugu Ueshima, Chao A. Hsiung, Jinrui Cui, Wayne H.H. Sheu, Jerome I. Rotter, Yii Der I. Chen, Chris Hsu, Yukinori Okada, Michiaki Kubo, Atsushi Takahashi, Toshihiro Tanaka, Frank J.A. Van Rooij, Santhi K. Ganesh, Jinyan Huang, Tao Huang, Jianmin Yuan, Joo Yeon Hwang, Myron D. Gross, Themistocles L. Assimes, Tetsuro Miki, Xiao Ou Shu, Lu Qi, Yuan Tson Chen, Xu Lin, Tin Aung, Tien Yin Wong, Yik Ying Teo, Bong Jo Kim, Norihiro Kato, E. Shyong Tai

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2551-2562
Number of pages12
JournalDiabetes
Volume63
Issue number7
DOIs
StatePublished - Jul 2014

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Chen, P., Takeuchi, F., Lee, J. Y., Li, H., Wu, J. Y., Liang, J., Long, J., Tabara, Y., Goodarzi, M. O., Pereira, M. A., Kim, Y. J., Go, M. J., Stram, D. O., Vithana, E., Khor, C. C., Liu, J., Liao, J., Ye, X., Wang, Y., ... Tai, E. S. (2014). Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians. Diabetes, 63(7), 2551-2562. https://doi.org/10.2337/db13-1815