Serum 25(OH)D levels are causally linked to height in European population: A mendelian randomization study

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To explore the causal relationship between serum vitamin D status and height, given that adequate vitamin D is essential for individuals to achieve their genetic height potential. A Mendelian randomization (MR) study was conducted. Instrumental variables (IVs) were derived from genome-wide association studies (GWASs) summary statistics to estimate levels of vitamin D, 25-hydroxyvitamin D (25(OH)D), and vitamin D binding protein. Inverse variance weighted (IVW) method and MR-Radial analyses were used to assess the causal association between vitamin D levels and height in mixed populations, as well as in male and female subgroups. Sensitivity analyses were performed to verify the robustness of the findings. Under the IVW random-effects model, higher 25(OH)D levels were significantly associated with increased height all groups: mixed population ( beta = 0.079, 95% CI 0.028 to 0.130, p = 0.002), females ( beta = 0.078, 95% CI 0.016 to 0.140, p = 0.013), and males ( beta = 0.072, 95% CI 0.019 to 0.128, p = 0.008). Additional analyses accounting for potential biases from outliers, pleiotropy, and confounding variables yielded consistent results. These findings indicated a genetic association between higher serum 25(OH)D levels and increased height, supporting the role of vitamin D in height determination among European populations. This study investigated the causal relationship between vitamin D status and height in the European population under the premise of satisfying the three basic assumptions of Mendelian randomization analysis: relevance, independence, and exclusion. The findings indicated that in mixed gender populations, as well as male and female populations, high levels of 25(OH)D leads to a significant increase in individual height. • Uses Mendelian randomization with GWAS-derived IVs, avoiding confounding in observational studies and providing stronger causal evidence for vitamin D-height association. • In European population, per 1-SD increase in 25(OH)D level corresponded to an increase in height of 0.21–0.98 cm. • Multiple sensitivity analyses verified the robustness of the conclusions and reduced the impact of potential biases. • Provides genetic evidence for vitamin D's regulatory role in height development, offering references for optimizing its levels to realize genetic height potential.