rs9472138

This association study investigates 18 BMI-associated and 14 WHR-associated gene variants identified by prior GWAS in 6,039 Danish individuals from the Inter99 cohort. The study found that QPCTL rs2287019 C allele was associated with increased insulinogenic index (7.4%, p=4.0×10⁻⁷) and disposition index (5.6%, p=6.4×10⁻⁵), while LRP1B rs2890652 C allele was associated with insulin resistance (3.3% increase in HOMA-IR, p=0.0011). For WHR variants, LYPLAL1/SLC30A10 rs4846567 G allele carriers showed improved insulin sensitivity (5.2% lower HOMA-IR in women, p=0.00086), whereas VEGFA rs6905288 A allele carriers showed insulin resistance in women (3.7% increase in HOMA-IR, p=0.00036).

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 paper applies a bias correction method for odds ratio estimates from GWAS discovery data, demonstrating that the 'winner's curse' affects initial effect size estimates. The authors applied conditional maximum likelihood estimation to correct bias in GWAS findings from multiple complex diseases (breast cancer, colorectal cancer, lung cancer, prostate cancer, type I and II diabetes) and show that bias-adjusted odds ratios are substantially more consistent with subsequent replication studies, with selection-adjusted confidence intervals providing better uncertainty quantification than uncorrected estimates.

Replication study of 7 meta-analysis-derived type 2 diabetes susceptibility SNPs in 6,244 Japanese individuals across 3 independent populations. Only rs864745 in JAZF1 showed nominal association (OR 1.148, 95% CI 1.034-1.275, p=0.0098) but not after Bonferroni correction; other loci did not reach statistical significance, suggesting these European-identified variants have minor or absent effects in Japanese populations.