rs7957197

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.

Family-based study examining parent-of-origin effects (POE) on type 2 diabetes risk in 4,211 individuals from Botnia and 1,463 from the Hungarian Transdanubian Biobank. Three loci showed nominal POE, with the strongest signal at rs7578597 in THADA showing excess maternal transmission of the risk T allele to diabetic offspring (Botnia pPOE=0.01, HTB pPOE=0.045, combined pPOE=0.0006). Five CpG sites flanking rs7578597 showed differential methylation between diabetic and non-diabetic islets, supporting potential THADA imprinting. Meta-analysis confirmed association with type 2 diabetes (OR=1.24, 95% CI 1.12-1.36, p=1.96×10⁻⁵).

Of 40 SNPs previously associated with type 2 diabetes, 19 (48%) introduce or remove CpG sites. In 84 human pancreatic islet donors, all 16 analyzed CpG-SNPs showed statistically significant differential DNA methylation (p≤2.3×10⁻⁵). Several CpG-SNPs including rs391300 (SRR), rs5945326 (DUSP9), rs11708067 (ADCY5), rs5015480 (HHEX), rs13266634 (SLC30A8), rs1801214 (WFS1), rs564398 (CDKN2A), and rs2237895 (KCNQ1) were associated with differential gene expression, alternative splicing, or hormone secretion, suggesting DNA methylation-mediated mechanisms linking genetic variants to type 2 diabetes pathogenesis.