Phenome-wide Mendelian-randomization study of genetically determined vitamin D on multiple health outcomes using the UK Biobank study.
Adult
Age Distribution
Aged
Biological Specimen Banks
Blood Pressure
Body Mass Index
Databases, Factual
Depression
/ epidemiology
Diabetes Mellitus, Type 2
/ epidemiology
Female
Fractures, Bone
/ epidemiology
Genetic Predisposition to Disease
Genome-Wide Association Study
Health Behavior
Humans
Hypertension
/ epidemiology
Male
Mendelian Randomization Analysis
Middle Aged
Mortality
Myocardial Ischemia
/ epidemiology
Phenotype
Polymorphism, Single Nucleotide
Sexism
Socioeconomic Factors
United Kingdom
/ epidemiology
Vitamin D Deficiency
/ epidemiology
25(OH)D
Mendelian randomization
PheWAS
vitamin D
Journal
International journal of epidemiology
ISSN: 1464-3685
Titre abrégé: Int J Epidemiol
Pays: England
ID NLM: 7802871
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
accepted:
16
08
2019
pubmed:
14
9
2019
medline:
21
4
2020
entrez:
14
9
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
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.
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.
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.
Identifiants
pubmed: 31518429
pii: 5569493
doi: 10.1093/ije/dyz182
pmc: PMC6857754
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1425-1434Subventions
Organisme : Medical Research Council
ID : MC_UU_00007/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 22804
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C348/A18927
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_U127527198
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 12076
Pays : United Kingdom
Organisme : Worldwide Cancer Research
ID : 12-1087
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C31250/A22804
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U127527198
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K018647/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL133786
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0600237
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0600329
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the International Epidemiological Association.
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