{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:07:16Z","timestamp":1785236836766,"version":"3.55.0"},"reference-count":86,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 212557\/Z\/18\/Z"],"award-info":[{"award-number":["WT 212557\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research Senior Investigator","doi-asserted-by":"publisher","award":["NIHR202411"],"award-info":[{"award-number":["NIHR202411"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council","award":["MC_UU_00032\/1"],"award-info":[{"award-number":["MC_UU_00032\/1"]}]},{"name":"Medical Research Council","award":["MC_UU_00032\/2"],"award-info":[{"award-number":["MC_UU_00032\/2"]}]},{"name":"Medical Research Council","award":["MC_UU_00032\/3"],"award-info":[{"award-number":["MC_UU_00032\/3"]}]},{"name":"Medical Research Council","award":["MC_UU_00032\/4"],"award-info":[{"award-number":["MC_UU_00032\/4"]}]},{"name":"Medical Research Council","award":["MC_UU_00032\/5"],"award-info":[{"award-number":["MC_UU_00032\/5"]}]},{"name":"Medical Research Council","award":["MC_UU_00032\/6"],"award-info":[{"award-number":["MC_UU_00032\/6"]}]},{"name":"Medical Research Council","award":["MC_UU_00032\/7"],"award-info":[{"award-number":["MC_UU_00032\/7"]}]},{"name":"Medical Research Council","award":["MC_UU_12013\/1"],"award-info":[{"award-number":["MC_UU_12013\/1"]}]},{"name":"Medical Research Council","award":["MC_UU_12013\/2"],"award-info":[{"award-number":["MC_UU_12013\/2"]}]},{"name":"Medical Research Council","award":["MC_UU_12013\/3"],"award-info":[{"award-number":["MC_UU_12013\/3"]}]},{"name":"Medical Research Council","award":["MC_UU_12013\/4"],"award-info":[{"award-number":["MC_UU_12013\/4"]}]},{"DOI":"10.13039\/501100000883","name":"University of Bristol","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000883","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute for Health Research (NIHR) Bristol Biomedical Research Centre"},{"name":"the Government Department of Business, Energy and Industrial Strategy"},{"DOI":"10.13039\/501100000361","name":"British Heart Foundation and Diabetes UK","doi-asserted-by":"publisher","award":["SBF006\\1117"],"award-info":[{"award-number":["SBF006\\1117"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"MRC Skills Development Fellowship","doi-asserted-by":"publisher","award":["MR\/P014054\/1"],"award-info":[{"award-number":["MR\/P014054\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Bristol Vice-Chancellor\u2019s Fellowship"},{"DOI":"10.13039\/501100007155","name":"MRC programme","doi-asserted-by":"publisher","award":["MC_UU_00011\/7"],"award-info":[{"award-number":["MC_UU_00011\/7"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Various vitamins and minerals have been implicated in the aetiology of depression. Objective: To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomisation (MR), a method using genetic data to estimate causal effects given certain assumptions. Methods: We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566) and rMDD (cases = 17,451; controls = 62,482). Results: None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g., cIVW) highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (ORcIVW 0.90 per SD increase; 95% CI 0.85\u20130.95; p = 0.0003); erythrocyte copper (ORcIVW 0.97; 95% CI 0.95\u20130.99; p = 0.0004); and 25(OH) vitamin D (ORcIVW 0.81; 0.66\u20130.99; p = 0.04). Apparent adverse effects of increased selenium on the risk of MDD (ORcIVW 1.03; 95% CI 1.02\u20131.05; p = 0.0003) and rMDD (ORcIVW 1.08; 95% CI 1.00\u20131.08; p = 0.06), and serum magnesium on rMDD (ORcIVW 1.21; 1.01\u20131.44; p = 0.04); were less consistent between methods and may be driven by pleiotropy. Conclusions: Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess.<\/jats:p>","DOI":"10.3390\/nu16213690","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T12:09:18Z","timestamp":1730203758000},"page":"3690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Micronutrients and Major Depression: A Mendelian Randomisation Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5504-1414","authenticated-orcid":false,"given":"Rebecca E.","family":"Carnegie","sequence":"first","affiliation":[{"name":"Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK"},{"name":"Medical Research Centre (MRC), Integrative Epidemiology Unit (IEU), University of Bristol, Bristol BS8 1QU, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Medical Research Centre (MRC), Integrative Epidemiology Unit (IEU), University of Bristol, Bristol BS8 1QU, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1QU, UK"},{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Borges","sequence":"additional","affiliation":[{"name":"Medical Research Centre (MRC), Integrative Epidemiology Unit (IEU), University of Bristol, Bristol BS8 1QU, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5883-9605","authenticated-orcid":false,"given":"Hannah J.","family":"Jones","sequence":"additional","affiliation":[{"name":"Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK"},{"name":"Medical Research Centre (MRC), Integrative Epidemiology Unit (IEU), University of Bristol, Bristol BS8 1QU, UK"},{"name":"NIHR Biomedical Research Centre, a Partnership between University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin H.","family":"Wade","sequence":"additional","affiliation":[{"name":"Medical Research Centre (MRC), Integrative Epidemiology Unit (IEU), University of Bristol, Bristol BS8 1QU, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M.","family":"Sallis","sequence":"additional","affiliation":[{"name":"Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK"},{"name":"Medical Research Centre (MRC), Integrative Epidemiology Unit (IEU), University of Bristol, Bristol BS8 1QU, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1QU, UK"},{"name":"School of Psychological Science, University of Bristol, Bristol BS8 1TU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4311-6890","authenticated-orcid":false,"given":"Sarah J.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1QU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Medical Research Centre (MRC), Integrative Epidemiology Unit (IEU), University of Bristol, Bristol BS8 1QU, UK"},{"name":"The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia"},{"name":"Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana A.","family":"Revez","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-640X","authenticated-orcid":false,"given":"Jonathan","family":"Evans","sequence":"additional","affiliation":[{"name":"Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Martin","sequence":"additional","affiliation":[{"name":"Medical Research Centre (MRC), Integrative Epidemiology Unit (IEU), University of Bristol, Bristol BS8 1QU, UK"},{"name":"Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 1QU, UK"},{"name":"NIHR Biomedical Research Centre, a Partnership between University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.clnu.2022.02.015","article-title":"ESPEN micronutrient guideline","volume":"41","author":"Berger","year":"2022","journal-title":"Clin. 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