{"doi":"10.1038/s41598-021-97679-5","title":"An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>A growing body of evidence suggests that vitamin D deficiency has been associated with an increased susceptibility to viral and bacterial respiratory infections. In this study, we aimed to examine the association between vitamin D and COVID-19 risk and outcomes. We used logistic regression to identify associations between vitamin D variables and COVID-19 (risk of infection, hospitalisation and death) in 417,342 participants from UK Biobank. We subsequently performed a Mendelian Randomisation (MR) study to look for evidence of a causal effect. In total, 1746 COVID-19 cases (399 deaths) were registered between March and June 2020. We found no significant associations between COVID-19 infection risk and measured 25-OHD levels after adjusted for covariates, but this finding is limited by the fact that the vitamin D levels were measured on average 11 years before the pandemic. Ambient UVB was strongly and inversely associated with COVID-19 hospitalization and death overall and consistently after stratification by BMI and ethnicity. We also observed an interaction that suggested greater protective effect of genetically-predicted vitamin D levels when ambient UVB radiation is stronger. The main MR analysis did not show that genetically-predicted vitamin D levels are causally associated with COVID-19 risk (OR = 0.77, 95% CI 0.55–1.11, P = 0.160), but MR sensitivity analyses indicated a potential causal effect (weighted mode MR: OR = 0.72, 95% CI 0.55–0.95, P = 0.021; weighted median MR: OR = 0.61, 95% CI 0.42–0.92, P = 0.016). Analysis of MR-PRESSO did not find outliers for any instrumental variables and suggested a potential causal effect (OR = 0.80, 95% CI 0.66–0.98, p-val = 0.030). In conclusion, the effect of vitamin D levels on the risk or severity of COVID-19 remains controversial, further studies are needed to validate vitamin D supplementation as a means of protecting against worsened COVID-19.</jats:p>","journal":"Scientific Reports","year":2021,"id":612108,"datarank":1.1368015777336347,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.636970901207354,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.636970901207354,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":24,"citers_with_citation_signal":24,"citers_with_endowment":24,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1575863,"name":"Jos van Geffen","orcid":null,"position":1,"is_corresponding":false},{"id":1575866,"name":"Michiel van Weele","orcid":null,"position":2,"is_corresponding":false},{"id":576031,"name":"Xiaomeng Zhang","orcid":"0000-0002-3794-6823","position":3,"is_corresponding":false},{"id":42122,"name":"Yazhou He","orcid":"0000-0003-2358-0143","position":4,"is_corresponding":false},{"id":1439,"name":"Xiangrui Meng","orcid":"0000-0003-4889-4640","position":5,"is_corresponding":false},{"id":1438,"name":"Maria Timofeeva","orcid":"0000-0002-2503-4253","position":6,"is_corresponding":false},{"id":227075,"name":"Harry Campbell","orcid":"0000-0002-6169-6262","position":7,"is_corresponding":false},{"id":1575873,"name":"Malcolm Dunlop","orcid":null,"position":8,"is_corresponding":false},{"id":92177,"name":"Lina Zgaga","orcid":"0000-0003-4089-9703","position":9,"is_corresponding":false},{"id":1575876,"name":"Evropi Theodoratou","orcid":null,"position":10,"is_corresponding":false},{"id":913388,"name":"Xue Li","orcid":"0000-0001-7073-7532","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"An observational and Mendelian randomisation study on vitamin D and COVID-19 risk in UK Biobank","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>A growing body of evidence suggests that vitamin D deficiency has been associated with an increased susceptibility to viral and bacterial respiratory infections. In this study, we aimed to examine the association between vitamin D and COVID-19 risk and outcomes. We used logistic regression to identify associations between vitamin D variables and COVID-19 (risk of infection, hospitalisation and death) in 417,342 participants from UK Biobank. We subsequently performed a Mendelian Randomisation (MR) study to look for evidence of a causal effect. In total, 1746 COVID-19 cases (399 deaths) were registered between March and June 2020. We found no significant associations between COVID-19 infection risk and measured 25-OHD levels after adjusted for covariates, but this finding is limited by the fact that the vitamin D levels were measured on average 11 years before the pandemic. Ambient UVB was strongly and inversely associated with COVID-19 hospitalization and death overall and consistently after stratification by BMI and ethnicity. We also observed an interaction that suggested greater protective effect of genetically-predicted vitamin D levels when ambient UVB radiation is stronger. The main MR analysis did not show that genetically-predicted vitamin D levels are causally associated with COVID-19 risk (OR = 0.77, 95% CI 0.55–1.11, P = 0.160), but MR sensitivity analyses indicated a potential causal effect (weighted mode MR: OR = 0.72, 95% CI 0.55–0.95, P = 0.021; weighted median MR: OR = 0.61, 95% CI 0.42–0.92, P = 0.016). Analysis of MR-PRESSO did not find outliers for any instrumental variables and suggested a potential causal effect (OR = 0.80, 95% CI 0.66–0.98, p-val = 0.030). In conclusion, the effect of vitamin D levels on the risk or severity of COVID-19 remains controversial, further studies are needed to validate vitamin D supplementation as a means of protecting against worsened COVID-19.</jats:p>","is_dataset_classified":null,"base_score":3.332204510175204,"endowment":3.332204510175204,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34521884","pmcid":"PMC8440633","openalex_id":"https://openalex.org/W3200026456","authors":[],"funders":[{"funder_name":"Cancer Research UK","grant_id":"C31250/A22804","title":null},{"funder_name":"Cancer Research UK","grant_id":"DRCPGM\\100012","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_PC_U127527198","title":null},{"funder_name":"Cancer Research UK","grant_id":"12076","title":null},{"funder_name":"Cancer Research UK","grant_id":"18927","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_UU_00007/1","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_PC_17228","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_QA137853","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_U127527198","title":null}],"total_grants":9,"fwci":3.1293,"citation_percentile":0.92572303,"influential_citations":0,"citation_trend":[{"year":2022,"count":10},{"year":2023,"count":5},{"year":2024,"count":7},{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/s41598-021-97679-5.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/s41598-021-97679-5.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/s41598-021-97679-5","host_type":"publisher"},{"url":"https://doi.org/10.1038/s41598-021-97679-5","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34521884","host_type":"repository"},{"url":"https://portal.findresearcher.sdu.dk/da/publications/80283230-a5e9-4190-a0f5-e91c08bd7551","host_type":"repository"},{"url":"https://doaj.org/article/b07a668bd137405998dfac0694e75f8e","host_type":"repository"},{"url":"http://europepmc.org/pmc/articles/PMC8440633","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8440633","host_type":"repository"},{"url":"https://hdl.handle.net/20.500.11820/e911c4d0-e807-47f7-b171-e77ad9d2f01d","host_type":"repository"},{"url":"https://www.research.ed.ac.uk/en/publications/e911c4d0-e807-47f7-b171-e77ad9d2f01d","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8440633","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8440633?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Vitamin D Research Studies","Genetic Associations and Epidemiology","COVID-19 Clinical Research Studies"],"mesh_terms":["COVID-19","SARS-CoV-2","Aged","Calcifediol","Female","United Kingdom","Humans","Male","Middle Aged","Prospective Studies","Risk Factors","Logistic Models","Odds Ratio","Biological Specimen Banks","Mendelian Randomization Analysis"],"keywords":["Biobank","Observational study","Coronavirus disease 2019 (COVID-19)","Medicine","2019-20 coronavirus outbreak","Mendelian inheritance","Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)","Bioinformatics","Internal medicine","Biology","Outbreak","Virology","Genetics","Gene","Disease"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"refsnp"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T01:36:18.778059Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}