All the risk alleles in the 11 examined type 2 diabetes risk variants showed an odds ratio (OR) greater than 1 for the GDM group compared with the control group ranging from 1.13 [95% confidence interval (CI) 0.88-1.46] to 1.44 (95% CI 1.19-1.74) except for the WFS1rs10010131 variant with OR 0.87 (95% CI 0.73-1.05).
As common WFS1 gene variants have recently been shown to confer a risk of type 2 diabetes, our findings may be relevant to the gradual but progressive loss of beta cells in type 2 diabetes.
While FTO rs8050136 and rs17817449, ADAMTS9 rs4607103, and WFS1rs10010131 were initially associated with T2DM, this was lost upon multiple testing correction.
Rare mutations in WFS1 cause Wolfram syndrome; using a gene-centric approach, we show that variation in WFS1 also predisposes to common type 2 diabetes.
Not only did an association between WFS1-rs6446482 and early-onset T2D exist in the subgroup analysis, but TCF2-rs7501939 and WFS1-rs6446482 were also confirmed to confer risk for T2D in this meta-analysis.
The most frequent haplotype at the haplotype block containing the WFS1 gene modulated insulin secretion and was associated with an increased risk of type 2 diabetes.
Of the 18 polymorphisms, the ADAMTS9, CDKAL1, CDKN2A/B-rs1412829, FTO, IGF2BP2, JAZF1, SLC30A8, TCF7L2, and WFS1 variants were associated with type 2 diabetes risk in our population.
Genetic variants of WFS1, CDKAL1, CDKN2BAS, TCF7L2, HHEX, KCNQ1, TSPAN8/LGR5, FTO, and TCF2 were associated with the risk for T2D with MetS, as well as the risk for development of T2D with at least one of the MetS components (P < 0.05).
We could show that 12 (57%) (HHEX, HNF1B, IGF2BP2, IRS1, KCNJ11, KCNQ1, NOTCH2, PPARG, TCF7L2, THADA, TSPAN8 and WFS1) out of 21 genes located in vicinity of these SNPs were showing aberrant expression in T2DM from the gene expression profiling studies.
Identification of a missense variant in the WFS1 gene that causes a mild form of Wolfram syndrome and is associated with risk for type 2 diabetes in Ashkenazi Jewish individuals.
T2D variants were associated with PCOS phenotype parameters including those in THADA and WFS1 with testosterone levels, ENPP/PC1 with triglyceride levels, FTO with glucose levels and KCNJ11 with FSH levels.