rs12785878

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 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.

This study examined associations between common variants in GC, CYP2R1, and NADSYN1/DHCR7 genes and plasma 25-hydroxyvitamin D levels in 3,210 Chinese Hans. Six variants showed significant associations with lower vitamin D levels: GC-rs4588 (β = -0.076 per risk-allele, P = 1.3 × 10⁻²⁶), GC-rs2282679 (β = -0.072, P = 4.9 × 10⁻²⁴), GC-rs7041, GC-rs1155563, NADSYN1/DHCR7-rs3829251 (β = -0.036, P = 4.7 × 10⁻⁵), and DHCR7-rs1790349 (β = -0.036, P = 5.7 × 10⁻⁵). Conditional analyses indicated that GC-rs4588 and GC-rs2282679 drive the associations at the GC locus in Chinese populations.

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.