| Title: | Phenome-wide association study of genetically predicted B vitamins and homocysteine biomarkers with multiple health and disease outcomes: analysis of the UK Biobank |
| Journal: | American Journal of Clinical Nutrition |
| Published: | 13 Jan 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36811473/ |
| DOI: | https://doi.org/10.1016/j.ajcnut.2023.01.005 |
Publication 10960
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Abstract
BACKGROUND: Although a number of health outcomes such as CVDs, metabolic-related outcomes, neurological disorders, pregnancy outcomes, and cancers have been identified in relation to B vitamins, evidence is of uneven quality and volume, and there is uncertainty about putative causal relationships.</p>
OBJECTIVES: To explore the effects of B vitamins and homocysteine on a wide range of health outcomes based on a large biorepository linking biological samples and electronic medical records.</p>
METHODS: First, we performed a phenome-wide association study (PheWAS) to investigate the associations of genetically predicted plasma concentrations (genetic component of the circulating concentrations) of folate, vitamin B6, vitamin B12, and their metabolite homocysteine with a wide range of disease outcomes (including both prevalent and incident events) among 385,917 individuals in the UK Biobank. Second, 2-sample Mendelian randomization (MR) analysis was used to replicate any observed associations and detect causality. We considered MR P <0.05 as significant for replication. Third, dose-response, mediation, and bioinformatics analyses were carried out to examine any nonlinear trends and to disentangle the underlying mediating biological mechanisms for the identified associations.</p>
RESULTS: In total, 1117 phenotypes were tested in each PheWAS analysis. After multiple corrections, 32 phenotypic associations of B vitamins and homocysteine were identified. Two-sample MR analysis supported that 3 of them were causal, including associations of higher plasma vitamin B6 with lower risk of calculus of kidney (OR: 0.64; 95% CI: 0.42, 0.97; P = 0.033), higher homocysteine concentration with higher risk of hypercholesterolemia (OR: 1.28, 95% CI: 1.04, 1.56; P = 0.018), and chronic kidney disease (OR: 1.32, 95% CI: 1.06, 1.63; P = 0.012). Significant nonlinear dose-response relationships were observed for the associations of folate with anemia, vitamin B12 with vitamin B-complex deficiencies, anemia and cholelithiasis, and homocysteine with cerebrovascular disease.</p>
CONCLUSIONS: This study provides strong evidence for the associations of B vitamins and homocysteine with endocrine/metabolic and genitourinary disorders.</p>
15 Authors
- Lijuan Wang
- Xue Li
- Azita Montazeri
- Amanda J MacFarlane
- Franco Momoli
- Susan Duthie
- Marjanne Senekal
- Ines Mesa Eguiagaray
- Ron Munger
- Derrick Bennett
- Harry Campbell
- Michele Rubini
- Helene McNulty
- Julian Little
- 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 |
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