{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T08:45:13Z","timestamp":1791794713950,"version":"4.3.4"},"reference-count":22,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008218","name":"Gangstedfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008218","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008208","name":"Overl\u00e6ge Johan Boserup og Lise Boserups Legat","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008208","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010358","name":"KV Fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010358","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003035","name":"Aase og Ejnar Danielsens Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003035","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Higher levels of plasma 25\u2010hydroxyvitamin D have been associated with a lower risk of age\u2010related macular degeneration (AMD). We investigated observational and potential causal associations of plasma 25\u2010hydroxyvitamin D with the risk of AMD in two large contemporary population\u2010based prospective studies and a genetic case\u2013control consortium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Observationally, we studied 25\u2009445 individuals with measured baseline plasma 25\u2010hydroxyvitamin D (536 incident AMD events) in the Copenhagen General Population Study (CGPS) and 372\u2009477 individuals (7842 incident AMD events) in the UK Biobank using Cox regression analysis for hazard ratios. Causally, we studied 107\u2009793 individuals (1474 incident AMD events) in the CGPS, 406861 individuals (9183 incident AMD events) in the UK Biobank and 31\u2009858 individuals (17\u2009411 AMD cases) in the International AMD Genomics Consortium with genetic variants leading to life\u2010long elevated plasma 25\u2010hydroxyvitamin D. These genetic variants were combined to plasma 25\u2010hydroxyvitamin D\u2010increasing unweighted and weighted allele scores and genetic associations to AMD risk were tested using Cox regression and logistic regression for hazard ratios and odds ratios.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Observationally, higher plasma 25\u2010hydroxyvitamin D was associated with higher AMD risk in CGPS and lower risk in UK Biobank. Genetically, each increase in the 25\u2010hydroxyvitamin D\u2010increasing weighted CGPS allele score was associated with a hazard ratio of 1.01 (95% confidence interval: 1.00\u20131.02) in CGPS, with similar results in the other studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings do not support a causal role of plasma 25\u2010hydroxyvitamin D in the risk of AMD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aos.70253","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T07:56:37Z","timestamp":1791791797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Higher plasma vitamin D levels are not causally associated with less age\u2010related macular degeneration"],"prefix":"10.1111","author":[{"given":"Sabina O.","family":"Beheshti","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry Copenhagen University Hospital\u2010Herlev and Gentofte  Herlev Denmark"},{"name":"The Copenhagen General Population Study Copenhagen University Hospital\u2010Herlev and Gentofte  Herlev Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Department of Ophthalmology Copenhagen University Hospital Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00f8rge G.","family":"Nordestgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Copenhagen University Hospital\u2010Herlev and Gentofte  Herlev Denmark"},{"name":"The Copenhagen General Population Study Copenhagen University Hospital\u2010Herlev and Gentofte  Herlev Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1442-4694","authenticated-orcid":false,"given":"Shoaib","family":"Afzal","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Copenhagen University Hospital\u2010Herlev and Gentofte  Herlev Denmark"},{"name":"The Copenhagen General Population Study Copenhagen University Hospital\u2010Herlev and Gentofte  Herlev Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1093\/hmg\/ddq155","article-title":"Genome\u2010wide association study of circulating vitamin D levels","volume":"19","author":"Ahn J.","year":"2010","journal-title":"Hum Mol Genet"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.m131","article-title":"Comparison of risk factor associations in UK biobank against representative, general population based studies with conventional response rates: prospective cohort study and individual participant meta\u2010analysis","volume":"368","author":"Batty G.D.","year":"2020","journal-title":"BMJ"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1161\/CIRCULATIONAHA.118.033470","article-title":"Relationship of familial hypercholesterolemia and high low\u2010density lipoprotein 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macular degeneration: a mendelian randomization study","volume":"120","author":"Dong X.\u2010X.","year":"2024","journal-title":"Am J Clin Nutr"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ng.3448","article-title":"A large genome\u2010wide association study of age\u2010related macular degeneration highlights contributions of rare and common variants","volume":"48","author":"Fritsche L.G.","year":"2016","journal-title":"Nat Genet"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1177\/1536867X1701700110","article-title":"The estimation and modeling of cause\u2010specific cumulative incidence functions using time\u2010dependent weights","volume":"17","author":"Lambert P.C.","year":"2017","journal-title":"Stata J"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1177\/1403494811401482","article-title":"The Danish National Patient Register","volume":"39","author":"Lynge 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