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Multiple Nonglycemic Genomic Loci Are Newly Associated With Blood Level of Glycated Hemoglobin in East Asians

2014; American Diabetes Association; Volume: 63; Issue: 7 Linguagem: Inglês

10.2337/db13-1815

1939-327X

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 N. Vithana, Chiea Chuen Khor, Jianjun Liu, Jiemin Liao, Xingwang Ye, Yiqin Wang, Ling Lu, Terri 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, Qibin Qi, Masato Isono, Wei Zheng, Qiuyin Cai, Yu‐Tang 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, Jian‐Min Yuan, Joo-Yeon Hwang, Myron D. Gross, Themistocles L. Assimes, Tetsuro Miki, Xiao‐Ou Shu, Qi Lu, Yuan-Tson Chen, Lin Xu, Tin Aung, Tien Yin Wong, Yik‐Ying Teo, Bong-Jo Kim, Norihiro Kato, E. Shyong Tai,

Diabetes and associated disorders

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.