Lijuan Wang
Phenome-wide association study of genetically predicted B vitamins and homocysteine biomarkers with multiple health and disease outcomes: analysis of the UK Biobank.
Wang, Lijuan; Li, Xue; Montazeri, Azita; MacFarlane, Amanda J.; Momoli, Franco; Duthie, Susan; Senekal, Marjanne; Eguiagaray, Ines Mesa; Munger, Ron; Bennett, Derrick; Campbell, Harry; Rubini, Michele; McNulty, Helene; Little, Julian; Theodoratou, Evropi
Authors
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
Abstract
Although a number of health outcomes such as cardiovascular diseases, 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. The objective of the study was 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. First, we performed a phenome-wide association study (PheWAS) to investigate 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, two-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 non-linear trends and to disentangle the underlying mediating biological mechanisms for the identified associations. In total 1,117 phenotypes were tested in each PheWAS analysis. After multiple correction, 32 phenotypic associations of B vitamins and homocysteine were identified. Two-sample MR analysis supported that three 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. This study provides strong evidence for the associations of B vitamins and homocysteine with endocrine/metabolic and genitourinary disorders.
Citation
WANG, L., LI, X., MONTAZERI, A., MACFARLANE, A.J., MOMOLI, F., DUTHIE, S., SENEKAL, M., EGUIAGARAY, I.M., MUNGER, R., BENNETT, D., CAMPBELL, H., RUBINI, M., MCNULTY, H., LITTLE, J. and THEODORATOU, E. 2023. Phenome-wide association study of genetically predicted B vitamins and homocysteine biomarkers with multiple health and disease outcomes: analysis of the UK Biobank. American journal of clinical nutrition [online], 117(3), pages 564-575. Available from: https://doi.org/10.1016/j.ajcnut.2023.01.005
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 9, 2023 |
Online Publication Date | Jan 13, 2023 |
Publication Date | Mar 31, 2023 |
Deposit Date | Jan 13, 2023 |
Publicly Available Date | Jan 14, 2024 |
Journal | American journal of clinical nutrition |
Print ISSN | 0002-9165 |
Electronic ISSN | 1938-3207 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 117 |
Issue | 3 |
Pages | 564-575 |
DOI | https://doi.org/10.1016/j.ajcnut.2023.01.005 |
Keywords | B vitamins; Homocysteine; PheWAS; Mendelian randomization |
Public URL | https://rgu-repository.worktribe.com/output/1854594 |
Related Public URLs | https://rgu-repository.worktribe.com/output/1854616 |
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Publisher Licence URL
https://creativecommons.org/licenses/by-nc-nd/4.0/
Copyright Statement
© 2023 Published by Elsevier Inc. on behalf of American Society for Nutrition.
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