| Title: | General and Sex-Specific Effects of Vitamin D Against Atrial Fibrillation and Young-Onset Ischemic Stroke: A Mendelian Randomization Series |
| Journal: | Journal of Clinical Biochemistry and Nutrition |
| Published: | 12 Jul 2024 |
| DOI: | https://doi.org/10.3164/jcbn.24-79 |
Publication 11661
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Background: Whether vitamin D deficiency causes atrial fibrillation and ischemic stroke of young onset <50 years was unknown.Methods: We derived a Genetic Risk Score for vitamin D by high-throughput exome chip analysis from 3922 subjects in the University of Hong Kong-Theme Based Research Cohort (rs2060793, rs4588, rs7041, [F-statistic=50.5, P<0.001]), and applied it in an independent sample of 1297 Chinese subjects (age: 67.0 ±10.6 years, 73% male) on clinical outcomes. Primary endpoint was a composite of atrial fibrillation and/ or ischemic stroke. A second study was performed to investigate generalisability and sex-specific effects in the UK Biobank (n=392,010; 46% men; 14,878 atrial fibrillation and 4,050 ischemic stroke cases, versus 374,102 controls).Results: After follow-up over 76±46 months, 240 primary endpoints (18.5%) were adjudicated. Higher genetically-predicted vitamin D independently predicted reduced odds of atrial fibrillation and/or ischemic stroke (OR=0.83 [0.72 to 0.95], P=0.008). Mendelian randomization analyses indicated vitamin D was causally protective against primary endpoint in Chinese (OR=0.81 [95%CI: 0.65 to 0.98]). An independent analysis in the UK Biobank revealed that vitamin D was generally protective against pre-specified young-onset ischemic stroke <50 years and atrial fibrillation combined (Odds ratio=0.36 [95%CI 0.14 to 0.94]), with predominant effect amongst men (Odds ratio=0.28 [95%CI 0.09 to 0.91]) compared to women (Odds ratio=0.60 [95%CI: 0.11 to 3.22]).Conclusions: Vitamin D may protect against young-onset ischemic stroke through preventing atrial fibrillation. Investigating the sex-specifc effects of vitamin D deficiency may potentially elucidate sex disparities of atrial fibrillation in the young.</p>
13 Authors
- Yap-Hang Chan
- Jie V Zhao
- C. Mary Schooling
- Shiu-Lun Au Yeung
- Yuen-Kwun Wong
- Ka-Wing Au
- Clara S Tang
- Chloe YY Cheung
- Aimin Xu
- Pak-Chung Sham
- Tai-Hing Lam
- Karen Siu-Ling Lam
- Hung-Fat Tse
1 Application
| Application ID | Title |
|---|---|
| 42468 | Non-reproductive effects of endogenous androgen exposures, potential drivers of and downstream factors related to androgens: a Mendelian randomization study in the UK Biobank |
Enabling scientific discoveries that improve human health