rs35767

Transethnic fine-mapping study of glycaemic traits in 26,760 participants (Hispanic/Latino, African, Asian, and Native American) using the Metabochip. Replicated 31/39 fasting glucose and 14/17 fasting insulin loci from European GWAS. Identified two novel secondary signals at G6PC2-rs477224 and GCK-rs2908290, a population-specific signal at G6PC2-rs77719485 in African ancestry, and one novel locus at SLC17A2-rs75862513 for fasting insulin.

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.

This study analyzed 521 SNPs in 18 insulin and IGF pathway genes among 1,439 subjects from two chemoprevention trials to identify genetic interactions associated with metachronous colorectal neoplasia. Classification and regression tree (CART) analysis identified gene-by-gene interactions: carriers of the A allele at rs7166348 (IGF1R) with AA genotype at rs1823023 (PIK3R1) had the highest probability of adenoma (71.8%, OR 3.7; 95%CI 2.2-6.5), while those with A at rs7166348, G at rs1823023, and AA at rs10426094 (INSR) had the lowest risk (14.3%, OR 0.22; 95%CI 0.07-0.66). Multifactor dimensionality reduction identified a three-way interaction (rs7166348, rs12609995, rs2715425) with OR 2.12 (95%CI 1.70-2.65) for metachronous neoplasia.

This study investigated the association between common genetic variation in IGF1, IGFBP1, and IGFBP3 genes and mammographic density in 819 women from the Multiethnic Cohort. Only weak evidence was found for associations: rs35767 (IGF1, p=0.03) was associated with 3.2% lower mammographic density, rs35539615 (IGFBP1, p=0.05) with higher density, and rs2453839 (IGFBP3, p=0.01) with lower density. Ethnicity significantly modified the associations for IGFBP3 variants.

This association study examined the IGF1 promoter SNP rs35767 (-C1245T) in 2,999 elderly adults (ages 70-79) from the Health ABC cohort and 483 younger adults (mean age 24.6) from the FMS cohort. The CC genotype was associated with increased body fat (2-3% higher in white women, P < 0.05) and decreased lean mass/muscle mass (3% lower in black women, P < 0.05) in elderly participants, but associations were much weaker in younger subjects. Associations were also found with reduced muscle strength in white women and lower bone mineral density in black women.