Abstract
Glycated haemoglobin (HbA1c) is widely used as a biomarker for the diagnosis of diabetes, for population-level screening, and for monitoring the glycaemic status during medical treatment. Although the heritability of HbA1c has been estimated at ~55-75%, a much smaller proportion of phenotypic variance is explained by the HbA1c-associated variants identified so far. To search for novel loci influencing the HbA1c levels, we conducted a genome-wide meta-analysis of 2 non-diabetic Japanese populations (n = 7,704 subjects in total). We identified 2 novel loci that achieved genome-wide significance: TMC6-TMC8 (P = 5.3 × 10-20) and SIX3-SIX2 (P = 8.6 × 10-9). Data from the largest-scale European GWAS conducted for HbA1c supported an association between the novel TMC6-TMC8 locus and HbA1c (P = 2.7 × 10-3). The association analysis with glycated albumin and glycation gap conducted using our Japanese population indicated that the TMC6-TMC8 and SIX3-SIX2 loci may influence the HbA1c level through non-glycaemic and glycaemic pathways, respectively. In addition, the pathway-based analysis suggested that the linoleic acid metabolic and 14-3-3-mediated signalling pathways were associated with HbA1c. These findings provide novel insights into the molecular mechanisms that modulate the HbA1c level in non-diabetic subjects.
Original language | English |
---|---|
Article number | 16147 |
Journal | Scientific reports |
Volume | 7 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2017 Dec 1 |
ASJC Scopus subject areas
- General