rs10941679

This functional study identifies rs3761124 as a causal variant on 20q13.33 that modulates glioma risk through enhancer activity and altered expression of multiple genes, particularly STMN3. Using luciferase assays, CRISPR-Cas9 editing, and eQTL analysis across 646 individuals from brain tissue and tumor cohorts, the authors demonstrate that rs3761124 has allele-specific effects on enhancer activity and consistently associates with STMN3 expression. Colocalization analysis (PP4=0.82) supports rs3761124 as the causal variant underlying the GWAS signal at this locus.

This systematic review examines FGF10 (fibroblast growth factor 10) pathogenic variants and their phenotypic effects across multiple organ systems, spanning from rare developmental disorders (lacrimal/salivary gland aplasia, lethal lung dysplasia) to common complex traits including chronic obstructive pulmonary disease, myopia, cleft lip/palate, and various cancers. The paper integrates functional data on FGF10 as an FGFR2b-specific ligand with a comprehensive catalog of reported variants and their clinical associations across human and animal studies.

A two-phase association study of 1,414 SNPs in steroid hormone and IGF-1 metabolism genes investigated breast cancer in situ (BCIS) risk in 1,062 cases and 10,126 controls from the Breast and Prostate Cancer Cohort Consortium. INSR-rs10500204 showed significant association with increased BCIS risk (OR=1.96 for homozygous major allele, p=1.68×10⁻⁵), being more strongly associated with BCIS than invasive disease. Two other SNPs (ACVR2A-rs2382112 and MAST2-rs12124649) showed nominally significant but less robust associations.

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

Population-based case-control study of 1,484 breast cancer cases and 1,307 controls examining 13 GWAS-identified SNPs for breast cancer susceptibility. Confirmed associations for 7 SNPs (rs13387042, rs4973768, rs10941679, rs2981582, rs3817198, rs3803662, rs6504950), with women in the highest quintile of a polygenic risk score having 2.2-fold increased breast cancer risk (95% CI: 1.67-2.88) compared to the lowest quintile. No significant interactions were detected between genetic loci and reproductive/menstrual risk factors.

This systematic review synthesizes current knowledge on FGF10-related disorders, covering the molecular mechanisms, tissue-specific expression patterns, and phenotypic spectrum of FGF10 abnormalities in humans. Key findings include that pathogenic variants in FGF10 cause congenital disorders (lacrimo-auriculo-dento-digital syndrome, aplasia of lacrimal and salivary glands, lethal lung developmental disorders) and that common SNPs in FGF10 are associated with increased risk of COPD (rs2973644, rs1011814, rs980510, rs10512844, rs10473352), myopia (rs339501, rs12517396), breast cancer (rs10941679), and cleft lip/palate (rs10462065).