4.3 Article

A comprehensive genetic and epidemiological association analysis of vitamin D with common diseases/traits in the UK Biobank

Journal

GENETIC EPIDEMIOLOGY
Volume 45, Issue 1, Pages 24-35

Publisher

WILEY
DOI: 10.1002/gepi.22357

Keywords

epidemiological association; Mendelian randomization; vitamin D

Funding

  1. National Natural Science Foundation of China [91746205]
  2. Yale World Scholars Program
  3. China Scholarship Council
  4. National Construction of High-level University Public Graduate Project

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Vitamin D has been extensively studied for its association with various diseases and traits in humans. Epidemiological and Mendelian randomization analyses have suggested potential causal relationships between vitamin D and health outcomes, including increased height and reduced risk of certain diseases like ovarian cancer and multiple sclerosis.
Vitamin D has been intensively studied for its association with human health, but the scope of such association and the causal role of vitamin D remain controversial. We aim to comprehensively investigate the links between vitamin D and human health through both epidemiological and Mendelian randomization (MR) analyses. We examined the epidemiological associations between serum 25-hydroxyvitamin D (25(OH)D) concentration and 90 diseases/traits in 326,409 UK Biobank (UKBB) Europeans. The causal relations between 25(OH)D and 106 diseases/traits were investigated by performing MR analysis using genome-wide significant 25(OH)D-associated variants (N = 143) from the largest UKBB GWAS to date. In epidemiological analysis, we found 25(OH)D was associated with 45 diseases/traits across cardiovascular/metabolic diseases, psychiatric/neurological diseases, autoimmune/inflammatory diseases, cancer, musculoskeletal diseases, and quantitative traits. In MR-analysis, we presented evidence suggesting potential causal role of 25(OH)D in increasing height (beta = .064, 95% confidence interval [CI] = 0.019-0.11) and preventing the risk of ovarian cancer (odds ratio [OR] = 0.96, 95% CI = 0.93-0.99), multiple sclerosis (OR = 0.96, 95% CI = 0.94-0.98), leg fracture (OR = 0.60, 95% CI = 0.45-0.80) and femur fracture (OR = 0.53, 95% CI = 0.32-0.84). These findings confirmed associations of vitamin D with a broad spectrum of diseases/traits and supported the potential causal role of vitamin D in promoting health.

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