Frontiers in Nutrition (Mar 2023)

Phenome-wide Mendelian randomization study evaluating the association of circulating vitamin D with complex diseases

  • Jin-jian Xu,
  • Jin-jian Xu,
  • Xiao-bin Zhang,
  • Wen-tao Tong,
  • Teng Ying,
  • Ke-qi Liu

DOI
https://doi.org/10.3389/fnut.2023.1108477
Journal volume & issue
Vol. 10

Abstract

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BackgroundCirculating vitamin D has been associated with multiple clinical diseases in observational studies, but the association was inconsistent due to the presence of confounders. We conducted a bidirectional Mendelian randomization (MR) study to explore the healthy atlas of vitamin D in many clinical traits and evaluate their causal association.MethodsBased on a large-scale genome-wide association study (GWAS), the single nucleotide polymorphism (SNPs) instruments of circulating 25-hydroxyvitamin D (25OHD) from 443,734 Europeans and the corresponding effects of 10 clinical diseases and 42 clinical traits in the European population were recruited to conduct a bidirectional two-sample Mendelian randomization study. Under the network of Mendelian randomization analysis, inverse-variance weighting (IVW), weighted median, weighted mode, and Mendelian randomization (MR)–Egger regression were performed to explore the causal effects and pleiotropy. Mendelian randomization pleiotropy RESidual Sum and Outlier (MR-PRESSO) was conducted to uncover and exclude pleiotropic SNPs.ResultsThe results revealed that genetically decreased vitamin D was inversely related to the estimated BMD (β = −0.029 g/cm2, p = 0.027), TC (β = −0.269 mmol/L, p = 0.006), TG (β = −0.208 mmol/L, p = 0.002), and pulse pressure (β = −0.241 mmHg, p = 0.043), while positively associated with lymphocyte count (β = 0.037%, p = 0.015). The results did not reveal any causal association of vitamin D with clinical diseases. On the contrary, genetically protected CKD was significantly associated with increased vitamin D (β = 0.056, p = 2.361 × 10−26).ConclusionThe putative causal effects of circulating vitamin D on estimated bone mass, plasma triglyceride, and total cholesterol were uncovered, but not on clinical diseases. Vitamin D may be linked to clinical disease by affecting health-related metabolic markers.

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