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

Chen P, Takeuchi F, Lee JY, Li H, Wu JY, Liang J, Long J, Tabara Y, Goodarzi MO, Pereira MA, Kim YJ, Go MJ, Stram DO, Vithana E, Khor CC, Liu J, Liao J, Ye X, Wang Y, Lu L, Young TL, Lee J, Thai AC, Cheng CY, van Dam RM, Friedlander Y, Heng CK, Koh WP, Chen CH, Chang LC, Pan WH, 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, Rotter JI, Chen YD, Hsu C, Okada Y, Kubo M, Takahashi A, Tanaka T, van Rooij FJ, Ganesh SK, Huang J, Huang T, Yuan J, Hwang JY, CHARGE Hematology Working Group, Gross MD, Assimes TL, Miki T, Shu XO, Qi L, Chen YT, Lin X, Aung T, Wong TY, Teo YY, Kim BJ, Kato N, Tai ES
Diabetes. 2014 63 (7): 2551-62

PMID: 24647736 · PMCID: PMC4284402 · DOI:10.2337/db13-1815

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.

© 2014 by the American Diabetes Association.

MeSH Terms (15)

Adult Aged Asian Continental Ancestry Group Blood Glucose Cohort Studies Far East Female Genetic Heterogeneity Genetic Loci Genome-Wide Association Study Glycated Hemoglobin A Humans Male Middle Aged Polymorphism, Single Nucleotide

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