| Title: | Causal relationship of serum 25-hydroxyvitamin D with chronic obstructive pulmonary disease: a prospective cohort and Mendelian randomization study |
| Journal: | Precision Nutrition |
| Published: | 25 Aug 2025 |
| DOI: | https://doi.org/10.1097/pn9.0000000000000112 |
| URL: | http://dx.doi.org/10.1097/pn9.0000000000000112 |
Publication 19669
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Abstract
The objective of this study is to assess the causal association between serum 25-hydroxyvitamin D [25(OH)D] and chronic obstructive pulmonary disease (COPD) risk in prospective cohort and Mendelian randomization (MR) frameworks, and examine the modifying effect of gene polymorphisms of vitamin D receptor (VDR) and vitamin D binding protein (VDBP) on this association. A total of 261,630 participants with serum 25(OH)D measurements and without prior COPD from the UK Biobank were included in the prospective cohort study, and 372,187 participants were included in the MR analyses. The study outcome was clinically diagnosed COPD. Serum 25(OH)D concentration was instrumented using 35 confirmed genome-wide significant variants. In the prospective cohort study, compared with participants with serum 25(OH)D <25 nmol/L, those with 25(OH)D of 25 to 50 nmol/L (adjusted hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.74-0.89) and ≥50 nmol/L (adjusted HR: 0.82; 95% CI: 0.74-0.91) had a significantly lower risk of new-onset COPD. A stronger inverse relationship of serum 25(OH)D with new-onset COPD was found among current smokers (P interaction = 0.015) and VDBP rs7041 CC allele carriers (vs. AA/AC alleles; P interaction = 0.028). VDBP rs7041 CC allele had a significantly higher risk of new-onset COPD (vs. AA/AC alleles; adjusted HR: 1.31; 95% CI: 1.08-1.58) in participants with serum 25(OH)D <25 nmol/L. MR revealed a nonlinear causal inverse association between 25(OH)D and COPD (P for nonlinearity <0.001), with COPD risk decreasing steeply as 25(OH)D concentration increases and leveling off around 50 nmol/L. Serum 25(OH)D showed a nonlinear inverse causal association with COPD risk, with optimal protection at ~50 nmol/L. Maintaining adequate vitamin D may be particularly important for genetically susceptible individuals and smokers.</p>
7 Authors
- Yuanyuan Zhang
- Yanjun Zhang
- Sisi Yang
- Yu Huang
- Ziliang Ye
- Xiaoqin Gan
- Xianhui Qin
1 Application
| Application ID | Title |
|---|---|
| 73201 | Identification of residual risks of non-infectious chronic diseases |
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