| Title: | Phenome-wide Mendelian-randomization study of genetically determined vitamin D on multiple health outcomes using the UK Biobank study |
| Journal: | International Journal of Epidemiology |
| Published: | 13 Sep 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/31518429/ |
| DOI: | https://doi.org/10.1093/ije/dyz182 |
| URL: | https://academic.oup.com/ije/article-pdf/48/5/1425/30802903/dyz182.pdf |
Publication 5533
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: Vitamin D deficiency is highly prevalent across the globe. Existing studies suggest that a low vitamin D level is associated with more than 130 outcomes. Exploring the causal role of vitamin D in health outcomes could support or question vitamin D supplementation.</p>
METHODS: We carried out a systematic literature review of previous Mendelian-randomization studies on vitamin D. We then implemented a Mendelian Randomization-Phenome Wide Association Study (MR-PheWAS) analysis on data from 339 256 individuals of White British origin from UK Biobank. We first ran a PheWAS analysis to test the associations between a 25(OH)D polygenic risk score and 920 disease outcomes, and then nine phenotypes (i.e. systolic blood pressure, diastolic blood pressure, risk of hypertension, T2D, ischaemic heart disease, body mass index, depression, non-vertebral fracture and all-cause mortality) that met the pre-defined inclusion criteria for further analysis were examined by multiple MR analytical approaches to explore causality.</p>
RESULTS: The PheWAS analysis did not identify any health outcome associated with the 25(OH)D polygenic risk score. Although a selection of nine outcomes were reported in previous Mendelian-randomization studies or umbrella reviews to be associated with vitamin D, our MR analysis, with substantial study power (>80% power to detect an association with an odds ratio >1.2 for per standard deviation increase of log-transformed 25[OH]D), was unable to support an interpretation of causal association.</p>
CONCLUSIONS: We investigated the putative causal effects of vitamin D on multiple health outcomes in a White population. We did not support a causal effect on any of the disease outcomes tested. However, we cannot exclude small causal effects or effects on outcomes that we did not have enough power to explore due to the small number of cases.</p>
27 Keywords
- Adult
- Age Distribution
- Aged
- Biological Specimen Banks
- Blood Pressure
- Body Mass Index
- Databases, Factual
- Depression
- Diabetes Mellitus, Type 2
- Female
- Fractures, Bone
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Health Behavior
- Humans
- Hypertension
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Mortality
- Myocardial Ischemia
- Phenotype
- Polymorphism, Single Nucleotide
- Sexism
- Socioeconomic Factors
- United Kingdom
- Vitamin D Deficiency
17 Authors
- Xiangrui Meng
- Xue Li
- Maria N Timofeeva
- Yazhou He
- Athina Spiliopoulou
- Wei-Qi Wei
- Aliya Gifford
- Hongjiang Wu
- Timothy Varley
- Peter Joshi
- Joshua C Denny
- Susan M Farrington
- Lina Zgaga
- Malcolm G Dunlop
- Paul McKeigue
- Harry Campbell
- Evropi Theodoratou
1 Application
| Application ID | Title |
|---|---|
| 10775 | Phenome-wide association study (PheWAS) for the investigation of the associations between serum vitamin D levels and multiple health outcomes |
Enabling scientific discoveries that improve human health