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Genome-wide meta-analysis in Japanese populations identifies novel variants at the TMC6-TMC8 and SIX3-SIX2 loci associated with HbA 1c .
- Source :
-
Scientific reports [Sci Rep] 2017 Nov 23; Vol. 7 (1), pp. 16147. Date of Electronic Publication: 2017 Nov 23. - Publication Year :
- 2017
-
Abstract
- Glycated haemoglobin (HbA <subscript>1c</subscript> ) 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 HbA <subscript>1c</subscript> has been estimated at ~55-75%, a much smaller proportion of phenotypic variance is explained by the HbA <subscript>1c</subscript> -associated variants identified so far. To search for novel loci influencing the HbA <subscript>1c</subscript> 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 <superscript>-20</superscript> ) and SIX3-SIX2 (P = 8.6 × 10 <superscript>-9</superscript> ). Data from the largest-scale European GWAS conducted for HbA <subscript>1c</subscript> supported an association between the novel TMC6-TMC8 locus and HbA <subscript>1c</subscript> (P = 2.7 × 10 <superscript>-3</superscript> ). 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 HbA <subscript>1c</subscript> 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 HbA <subscript>1c</subscript> . These findings provide novel insights into the molecular mechanisms that modulate the HbA <subscript>1c</subscript> level in non-diabetic subjects.
- Subjects :
- Aged
Asian People genetics
Female
Genome-Wide Association Study
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide genetics
Homeobox Protein SIX3
Blood Glucose metabolism
Eye Proteins genetics
Glycated Hemoglobin metabolism
Homeodomain Proteins genetics
Membrane Proteins genetics
Nerve Tissue Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 29170429
- Full Text :
- https://doi.org/10.1038/s41598-017-16493-0