rs757210

This association study examined 43 diabetes-related SNPs in relation to diastolic dysfunction and cardiovascular disease across two Swedish cohorts. HNF1B rs757210 (T-allele) was the main finding, associated with prevalent diastolic dysfunction in both the discovery cohort (MPP-RES; OR 1.21, P=0.024) and replication cohort (VARA; OR 1.38, P=0.042), and with increased risk of incident CVD (HR 1.05, P=0.042) but not CHF over 30+ years of follow-up.

Association analysis of 31 GWAS-confirmed type 2 diabetes SNPs in 3,089 Indian sib pairs (2,528 for quantitative traits, 561 for diabetes) identified significant associations with intermediate traits: CDKAL1 rs7756992, TCF7L2 rs7903146 and rs12255372 with fasting glucose (β=0.009-0.01, p≤0.01); ADAM30 rs2641348, NOTCH2 rs10923931, TCF-2/HNF1B rs757210, and CDKN2A/B rs10811661 with fasting insulin and HOMA-IR (β=±0.05-0.09, p≤0.05); and THADA rs7578597 with type 2 diabetes (OR 1.5, p=0.03).

This GWAS of fasting glucose in the ARIC study examined 5,782-8,372 individuals across four longitudinal visits and identified five genomic regions significantly associated with fasting glucose (p < 5×10⁻⁸): GCKR, G6PC2, GCK, SLC30A8, and MTNR1B. The study demonstrated that averaging fasting glucose measures across visits improved statistical power and detected additional signals (GCKR rs780094, SLC30A8 rs13266634) not visible in single-visit analyses. Analysis of candidate SNPs revealed significant interactions with diabetes status: associations with fasting glucose were stronger in non-diabetic individuals than in those with prevalent diabetes for multiple SNPs including rs10830963 (MTNR1B), rs560887 (G6PC2), rs4607517 (GCK), and rs780094 (GCKR).