rs10741657

A bidirectional two-sample Mendelian randomization study examining the causal relationship between 25-hydroxyvitamin D levels and attention-deficit/hyperactivity disorder (ADHD). Using 79,366 European individuals for vitamin D GWAS data and 19,099 ADHD cases with 34,194 controls, the study found no evidence of a causal effect of vitamin D on ADHD (IVW β = -0.043, p = 0.833) or reverse causality. Although rs12785878 showed a nominal association with increased ADHD risk at higher vitamin D levels (p = 0.024), this did not survive multiple testing correction.

This case-control association study of 815 Chinese pregnant women identified five SNPs in the GC (vitamin D-binding protein) gene significantly associated with serum 25-hydroxyvitamin D concentration: rs17467825, rs4588, rs2282679, rs2298850, and rs1155563. Mean 25(OH)D level was 15.67±7.98 ng/mL with 75% prevalence of deficiency. An XGBoost model incorporating these SNPs plus environmental factors achieved AUC 0.828 for predicting 25(OH)D deficiency risk. The study suggests maternal vitamin D deficiency may increase macrosomia risk (12 of 16 macrosomic infants had deficient mothers).

This systematic review examines the role of cytochrome P450 (CYP) gene polymorphisms in the pathogenesis and development of ulcerative colitis. The authors discuss ten critical CYP isoforms (CYP1A1, CYP2D6, CYP2J2, CYP2R1, CYP3A4/3A5/3A7, CYP4F3, CYP24A1, CYP26B1, and CYP27B1) and their genetic variants associated with UC susceptibility and drug metabolism. Notable findings include CYP1A1*2A correlation with UC predisposition, CYP2D6*4 polymorphisms increasing UC risk (OR=1.56), CYP2J2 promoter polymorphism (G-50T) enrichment in UC patients, CYP24A1 variants (rs4809957, rs6068816, rs6091822, rs8124792) showing significant associations in East Asian populations, and CYP27B1 induction in UC lesions.

This study examined genetic variants in the vitamin D pathway using GWAS data from 3,686 women of African ancestry (1,657 cases). No significant associations were found between vitamin D pathway variants and breast cancer risk overall or by estrogen receptor status (pathway P > 0.5, SNP-level P adj > 0.2). Mendelian randomization analysis showed no association with genetically predicted 25(OH)D levels (P = 0.23). However, a nonsense variant rs41302073 in TYRP1 (pigment synthesis pathway) showed a 54% increased risk of breast cancer (OR = 1.54, 95% CI = 1.24-1.91, P adj = 0.007), warranting further investigation of non-vitamin D mechanisms.

This retrospective association study of 264 patients with stages II and III colon cancer examined genetic variants in vitamin D modulating genes and their association with time to recurrence (TTR). The GC rs2282679 GG genotype was significantly associated with decreased TTR (HR=3.64, p=0.027) in patients with surgery alone, while CYP2R1 rs10741657 showed a trend toward decreased TTR (HR=1.50, p=0.060). DHCR7 rs12785878 showed no significant association with TTR.

Genome-wide association analysis of circulating vitamin D (25(OH)D) levels in 572 Caucasian children with asthma identified SNPs nominally associated with vitamin D at baseline and year 4, with four SNPs replicated in 592 Costa Rican asthmatics (rs11002969, rs163221, rs1678849, rs4864976). Two major previous GWAS findings were replicated: rs2282679 (GC, p<1.9×10⁻¹⁰⁹ in original study) with strongest effect and rs10741657 (CYP2R1, p=3.3×10⁻²⁰) to a lesser degree, but these associations did not consistently replicate across all three populations including 516 Puerto Rican asthmatics.

This study examined whether genetic variants that predict higher 25-hydroxyvitamin D (25(OH)D) levels are associated with reduced multiple sclerosis (MS) risk in 1,655 MS cases and 6,349 controls. SNPs in GC (rs2282679) were significant predictors of 25(OH)D levels but showed no association with MS risk. The CYP2R1 rs10741657 'A' allele was associated with increased 25(OH)D and reduced MS risk among HLA-DR15 negative individuals (OR=0.89, 95% CI: 0.79-1.01) but not HLA-DR15 positive individuals. CYP27B1 rs703842 'C' allele was inversely associated with MS risk, with stronger effects in HLA-DR15 negative (OR=0.79, 95% CI: 0.69-0.90) versus positive individuals (OR=0.91, 95% CI: 0.80-1.04), suggesting vitamin D's protective effect on MS may be attenuated by the HLA-DR15 risk allele.