Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study
Butler-Laporte G, Nakanishi T, Mooser V, Morrison DR, Abdullah T, Adeleye O, Mamlouk N, Kimchi N, Afrasiabi Z, Rezk N, Giliberti A, Renieri A, Chen Y, Zhou S, Forgetta V, Richards JB
PLoS medicine · 97 citas
Cómo se estudió
- Diseño
- Estudio de casos y controles (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Wellcome Trust
- Gobierno
- Public Health Agency of Canada
- Gobierno
- Compute Canada
- Organización sin fines de lucro
- Cancer Research UK
- Gobierno
- National Institute for Health and Care Research
- Universidad u hospital
- King's College London
- Gobierno
- European Commission
- Gobierno
- Public Health Agency
- Gobierno
- Canada Excellence Research Chairs, Government of Canada
- Universidad u hospital
- Jewish General Hospital
- Gobierno
- National Institutes of Health
- Gobierno
- NIHR BioResource
- Gobierno
- Canadian Institutes of Health Research
- Gobierno
- Fonds de Recherche du Québec - Santé
- Gobierno
- Medical Research Council
- Gobierno
- Japan Society for the Promotion of Science
- Universidad u hospital
- Guy's and St Thomas' NHS Foundation Trust
- Gobierno
- Calcul Québec
- Universidad u hospital
- Lady Davis Institute of the Jewish General Hospital
- Gobierno
- NIH Foundation
- Gobierno
- Canadian Foundation for Innovation
- Gobierno
- Genome Québec
- Gobierno
- NIHR-BioResource
- Gobierno
- Fonds de Recherche du Québec - Santé and Québec Ministry of Health and Social Services
- Universidad u hospital
- Guy's and St Thomas' NHS Foundation Trust
- Subvenciones
- Canadian Institutes of Health Research (CIHR: 365825); Canadian Institutes of Health Research (CIHR: 365825; 409511); Canadian Institutes of Health Research (COVID-19); Canadian Institutes of Health Research (365825; 409511); Canadian Institutes of Health Research (40951_1); National Institutes of Health (COVID-19); Medical Research Council (MC_PC_17228); National Institute for Health and Care Research (COVID-19); European Commission (COVID-19); Canadian Institutes of Health Research (365825); Medical Research Council (COVID-19)
Según 25 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2021-06-01 · PLoS Med · vol. 18 · número 6 · pág. e1003605
- Editorial
- Public Library of Science
- Citado
- 127 citas · más que el 100% de estudios similares · 17.1× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 49 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Vitamin D Research Studies · Genetic Associations and Epidemiology · SARS-CoV-2 and COVID-19 Research
- Palabras clave
- vitamin D, 25-hydroxyvitamin D, COVID-19 susceptibility, COVID-19 severity, SARS-CoV-2, vitamin D deficiency, vitamin D supplementation, Mendelian randomization, genetic variants, hospitalization, severe illness, causal effects, horizontal pleiotropy, weak instrument bias, vitamin D receptor, CYP24A1, CYP8B1, CYP27B1, CYP3A4, CYP2R1, CYP27C1, CYP27A1
- MeSH
- humans, vitamin d deficiency, genetic predisposition to disease, vitamin d, hospitalization, severity of illness index, odds ratio, risk factors, case-control studies, causality, polymorphism, single nucleotide, dietary supplements, adult, aged, middle aged, female, male, genome-wide association study, mendelian randomization analysis, covid-19, sars-cov-2, white people
16 autores
- Guillaume Butler‐Laporte🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Tomoko Nakanishi🇯🇵🇨🇦Japan Society for the Promotion of Science; Kyoto University; Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Vincent Mooser🇨🇦McGill University
- David Morrison🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Tala Abdullah🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Olumide Adeleye🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Noor Mamlouk🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Nofar Kimchi🇮🇱🇨🇦Technion – Israel Institute of Technology; Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Zaman Afrasiabi🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Nardin Rezk🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Annarita Giliberti🇮🇹University of Siena
- Alessandra Renieri🇮🇹University of Siena; Azienda Ospedaliera Universitaria Senese
- Yiheng Chen🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Sirui Zhou🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- Vincenzo Forgetta🇨🇦Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
- John Brent Richards🇬🇧🇨🇦 · autor de correspondenciaKing's College London; Jewish General Hospital; Lady Davis Institute for Medical Research; McGill University
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
Increased vitamin D levels, as reflected by 25-hydroxy vitamin D (25OHD) measurements, have been proposed to protect against COVID-19 based on in vitro, observational, and ecological studies. However, vitamin D levels are associated with many confounding variables, and thus associations described to date may not be causal. Vitamin D Mendelian randomization (MR) studies have provided results that are concordant with large-scale vitamin D randomized trials. Here, we used 2-sample MR to assess evidence supporting a causal effect of circulating 25OHD levels on COVID-19 susceptibility and severity.
Methods and findings
Genetic variants strongly associated with 25OHD levels in a genome-wide association study (GWAS) of 443,734 participants of European ancestry (including 401,460 from the UK Biobank) were used as instrumental variables. GWASs of COVID-19 susceptibility, hospitalization, and severe disease from the COVID-19 Host Genetics Initiative were used as outcome GWASs. These included up to 14,134 individuals with COVID-19, and up to 1,284,876 without COVID-19, from up to 11 countries. SARS-CoV-2 positivity was determined by laboratory testing or medical chart review. Population controls without COVID-19 were also included in the control groups for all outcomes, including hospitalization and severe disease. Analyses were restricted to individuals of European descent when possible. Using inverse-weighted MR, genetically increased 25OHD levels by 1 standard deviation on the logarithmic scale had no significant association with COVID-19 susceptibility (odds ratio [OR] = 0.95; 95% CI 0.84, 1.08; p = 0.44), hospitalization (OR = 1.09; 95% CI: 0.89, 1.33; p = 0.41), and severe disease (OR = 0.97; 95% CI: 0.77, 1.22; p = 0.77). We used an additional 6 meta-analytic methods, as well as conducting sensitivity analyses after removal of variants at risk of horizontal pleiotropy, and obtained similar results. These results may be limited by weak instrument bias in some analyses. Further, our results do not apply to individuals with vitamin D deficiency.
Conclusions
In this 2-sample MR study, we did not observe evidence to support an association between 25OHD levels and COVID-19 susceptibility, severity, or hospitalization. Hence, vitamin D supplementation as a means of protecting against worsened COVID-19 outcomes is not supported by genetic evidence. Other therapeutic or preventative avenues should be given higher priority for COVID-19 randomized controlled trials.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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