Multiple Non-glycemic Genomic Loci Are Newly Associated with Blood Level of Glycated Hemoglobin in East Asians (original) (raw)

Glycated hemoglobin (HbA 1C ) is used as a measure of glycemic control and also as a diagnostic criterion for diabetes mellitus. To discover novel loci harbouring common variants associated with HbA 1C in East Asians, we conducted a meta-analysis of 13 genome wide association studies (N=21,026). We replicated our findings in 3 additional studies comprising 11,576 individuals of East Asian ancestry. 10 variants showed associations that reached genome wide significance in the discovery dataset of which 9 [4 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 5 variants at loci that had been previously identified (CDKAL1, G6PC2/ABCB11, GCK, ANK1, and FN3K)] showed consistent evidence of association in Page 7 of 75 For Peer Review Only Diabetes 9 © replication datasets. These variants explained 1.76% of the variance in HbA 1C. Several of these variants (TMEM79, HBS1L/MYB, CYBA, MYO9B, ANK1, and FN3K) showed no association with either blood glucose or type 2 diabetes. Amongst individuals with nondiabetic levels of fasting glucose (<7.0 mmol/l) but elevated (>=6.5%) HbA 1c , 36.1% had HbA1C<6.5% after adjustment for these 6 variants. . Our East Asian GWAS meta-analysis has identified novel variants associated with HbA 1C as well as demonstrating 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 HbA 1C for diagnosing diabetes in these populations.