rs7501939

Case-parent triad study of 366 pediatric and adolescent germ cell tumor (GCT) cases examining 26 SNPs from adult testicular GCT GWAS. Three variants reached multiple testing-corrected significance: SPRY4 rs4624820 (OR=0.70, protective), BAK1 rs210138 (OR=1.70, particularly strong for testicular tumors OR=3.31), and GAB2 rs948662 (OR=1.56). Maternal effects observed for KITLG rs4474514 (OR=1.66) and rs7221274 near TEX14/RAD51C/PPM1E (OR=1.63).

Genome-wide association study of 474 prostate cancer cases and 458 controls from West African men identified a novel prostate cancer susceptibility locus at 10p14 marked by rs7918885 (p=1.29×10⁻⁷), localized to an intron of the lncRNA gene RP11-543F8.2. A stratified analysis by Gleason score revealed additional associations including rs34575154 in PCDHA1 at 5q31.3 (p=3.66×10⁻⁸) for high-grade disease and rs985081 at Xq28 (p=8.66×10⁻⁹) for low-grade disease. Validation in the African Ancestry Prostate Cancer GWAS Consortium showed limited replication, with only rs2993385 at 10p14 reaching nominal significance (p<0.05), highlighting population-specific genetic architecture.

Case-control study of 127 African American prostate cancer cases and 345 controls from the Flint Men's Health Study examining 24 SNPs previously associated with prostate cancer in European populations. Found nominal evidence (P<0.05) for association with three 8q24 SNPs (rs6983561 OR=1.55, rs16901979 OR=1.60, rs7000448 OR=1.41) and two 10q11 SNPs (rs7904463, rs10740051 OR=0.51), replicating 8q24 findings in African Americans and providing first evidence for MSMB region association in this population.

Population-based study of 6,733 non-diabetic Finnish men examining associations between 19 confirmed type 2 diabetes risk loci and tissue-specific insulin resistance indices. Type 2 diabetes risk SNPs in KCNJ11 (rs5219) and HHEX (rs1111875) showed significant associations with lower liver insulin resistance (p<0.0013 and p=5.4×10⁻⁵, respectively), while the Pro12 allele of PPARG2 (rs1801282) was significantly associated with higher adipocyte insulin resistance (p=6.2×10⁻⁵).

A nested case-control study in two prospective cohorts (CPS-II and PLCO) examining whether HNF1B and JAZF1 variants associated with both diabetes and prostate cancer mediate the inverse relationship between these diseases. Three HNF1B SNPs (rs11649743, rs4430796, rs7501939) were associated with decreased prostate cancer risk (OR 0.84-0.86) and marginally increased diabetes risk, while two JAZF1 SNPs (rs6968704, rs10486567) were associated with decreased prostate cancer risk but not diabetes. The associations persisted after stratification by diabetic status, indicating that diabetes does not mediate the SNP-prostate cancer relationships.

This association study of 4,213 Danish individuals examined 25 type 2 diabetes risk variants and their association with birthweight. The study found that type 2 diabetes risk alleles near ADCY5 (rs11708067, β = -33 g, p = 0.004), CDKAL1 (rs7756992, β = -22 g, p = 0.04), and HHEX-IDE (rs1111875, β = -16 g in meta-analysis, p = 8×10⁻⁵, n = 25,164) were associated with reduced birthweight, supporting the fetal insulin hypothesis. Meta-analyses confirmed these associations and showed no strong general effect on birthweight from the 25 common type 2 diabetes risk alleles combined.

This comprehensive review examines genetic association studies on prostate cancer, discussing GWASs that have identified over 75 variants associated with PCa risk (as of February 2016), with major susceptibility regions at 8q24, 17q12, 17q24, 10q11, and 19q13. The paper also reviews candidate gene-based approaches targeting genes involved in androgen signaling, carcinogen metabolism, DNA repair, vitamin D signaling, inflammation, angiogenesis, and cellular adhesion, as well as regulatory RNA genes.

This case-control and family-based association study tested whether 18 type 2 diabetes susceptibility loci are associated with type 1 diabetes in 7,606 type 1 diabetic cases and 8,218 controls. Only PPARG (rs1801282/Pro12Ala, OR=0.91, p=0.004) and HHEX-IDE (rs1111875, OR=0.94, p=0.003) showed evidence of association with type 1 diabetes. The authors conclude that type 1 and type 2 diabetes do not share a common genetic background, supporting the view that type 1 diabetes is primarily an autoimmune disease.