Causal relationship between vitamin D and adult height: A bidirectional Mendelian randomization study

Vitamin D is critical for skeletal growth, but its causal link to adult height remains uncertain due to limitations in observational studies and randomized controlled trials. This study aimed to explore the bidirectional causal relationship between circulating vitamin D levels and adult height using Mendelian randomization (MR). A bidirectional 2-sample MR analysis was performed with large-scale genome-wide association study data. Vitamin D data were sourced from the Pan-UKB (n = 383,324 European individuals), and height data from FinnGen R12 (n = 364,629 Finnish individuals). Genetic instruments were selected based on genome-wide significance (P < 5 × 10-8) and independence (linkage disequilibrium r² < 0.001). Multiple MR approaches, including inverse variance weighted (IVW), MR-Egger, and weighted median, were applied, with sensitivity analyses to evaluate pleiotropy and heterogeneity. Genetically predicted higher vitamin D concentrations were associated with increased adult height, with each standard deviation increase in vitamin D corresponding to a 0.046 standard deviation height increase (P = 1.53 × 10-5, IVW method). Sensitivity analyses supported this finding, showing no directional pleiotropy. Conversely, no causal effect of height on vitamin D levels was detected (β = 0.008, P = .343, IVW method). This study provides genetic evidence supporting a modest causal effect of circulating vitamin D levels on adult height, with no evidence of reverse causality. These findings complement and extend prior randomized controlled trials evidence, highlighting the role of vitamin D in skeletal development while underscoring that supplementation alone is unlikely to yield substantial height gains in vitamin D-replete populations.