rs2383208

A case-control study of 443 T2D cases and 532 controls from a Russian population (HAPIEE cohort) investigating four polymorphisms as predictors of type 2 diabetes development over 10 years. rs7903146 in TCF7L2 was significantly associated with T2D risk (TT genotype RR 3.90, 95% CI 2.31-6.61; TC genotype RR 1.86, 95% CI 1.42-2.43; CC protective RR 0.37, 95% CI 0.29-0.49, all p<0.001). No significant associations were found for rs1799883 (FABP2), rs2237892 (KCNQ1), or rs6773957 (ADIPOQ). TCF7L2 rs7903146 retained significance in risk models for both men and women.

This comprehensive review examines the association between type 2 diabetes mellitus (T2DM) and multiple myeloma (MM) risk. Genetic variants linked to T2DM show opposite associations with MM compared to diabetes GWAS: variants like CDKN2A-2B rs2383208, IGF1 rs35767, KCNQ1 rs2237892, and MADD rs7944584 increase MM risk, while FTO rs8050136, KCNJ11 rs5215/rs5219, LTA rs1041981, and THADA rs7578597 decrease risk. The IGF1 rs35767 promoter polymorphism is strongly associated with MM risk via cell proliferation mechanisms. A meta-analysis of 20 observational studies (>3 million participants) found T2DM patients had OR=1.53 (95% CI, 1.30-1.81) for MM, and MetS patients had OR=1.39 (95% CI, 1.17-1.64), mediated through insulin resistance, hyperinsulinemia, inflammatory cytokines (IL-6, TNF-α, IL-1β), dyslipidemia, and acidosis pathways.

Transethnic genome-wide meta-analysis in 159,940 individuals identified 60 common genetic variants associated with HbA1c levels. Variants were classified as glycemic (19), erythrocytic (22), or unclassified (19) based on their biological mechanisms. Glycemic variants were associated with higher type 2 diabetes risk (OR=1.05 per allele, p=3×10⁻²⁹), while erythrocytic variants were not. The X-linked G6PD G202A variant showed a large effect in African Americans (0.81% HbA1c reduction per allele) but minimal effects in other ancestries, potentially causing 2% of African American T2D cases to remain undiagnosed when using HbA1c screening.

A replication study of genome-wide association findings in the CDKN2A/CDKN2B region on chromosome 9p in 3,093 French Europids (1,455 cases, 1,638 controls). The study confirms a strong association of rs10811661 with type 2 diabetes (p=3.8×10⁻⁷, OR 1.43 [95% CI 1.24-1.64]) and identifies rs3218018 as a secondary signal surviving Bonferroni correction (p=0.002). The rs564398 variant did not reach significance in this population.

Applied multilocus localized haplotype clustering to Wellcome Trust Case Control Consortium data (14,000 cases of 7 common diseases + 3,000 controls) to identify disease-associated loci with stronger evidence than single-marker tests. Identified three highly significant associations: 10p15.1 with type 1 diabetes (p=5.1×10⁻⁹), 12q15 with type 2 diabetes (p=1.9×10⁻⁷), and 15q26.2 with hypertension (p=2.8×10⁻⁸), plus 9p21.3 with type 2 diabetes (p=2.8×10⁻⁸). Stringent genotype quality filtering effectively removed false positives from genotyping artifacts.