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We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (<jats:italic>N<\/jats:italic>\u2009=\u2009246,139), total iron binding capacity (<jats:italic>N<\/jats:italic>\u2009=\u2009135,430), iron (<jats:italic>N<\/jats:italic>\u2009=\u2009163,511) and transferrin saturation (<jats:italic>N<\/jats:italic>\u2009=\u2009131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at <jats:italic>DUOX2<\/jats:italic>, <jats:italic>F5<\/jats:italic>, <jats:italic>SLC11A2<\/jats:italic> and <jats:italic>TMPRSS6<\/jats:italic> associate with iron deficiency anemia, while variants at <jats:italic>TF<\/jats:italic>, <jats:italic>HFE<\/jats:italic>, <jats:italic>TFR2<\/jats:italic> and <jats:italic>TMPRSS6<\/jats:italic> associate with iron overload. A <jats:italic>HBS1L-MYB<\/jats:italic> intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The <jats:italic>DUOX2<\/jats:italic> missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding\/menstruation.<\/jats:p>","DOI":"10.1038\/s42003-020-01575-z","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T11:10:36Z","timestamp":1612350636000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":158,"title":["A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6774-3149","authenticated-orcid":false,"given":"Steven","family":"Bell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas S.","family":"Rigas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8593-4934","authenticated-orcid":false,"given":"Magnus K.","family":"Magnusson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8090-7988","authenticated-orcid":false,"given":"Egil","family":"Ferkingstad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1634-8330","authenticated-orcid":false,"given":"Elias","family":"Allara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyda","family":"Bjornsdottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ramond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"S\u00f8rensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7067-9862","authenticated-orcid":false,"given":"Gisli H.","family":"Halldorsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8230-0116","authenticated-orcid":false,"given":"Dirk S.","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristoffer S.","family":"Burgdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1674-9978","authenticated-orcid":false,"given":"Hannes P.","family":"Eggertsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7618-0050","authenticated-orcid":false,"given":"Joanna M. 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Lancet 390, 2360\u20132371 (2017).","journal-title":"Lancet"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01575-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01575-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01575-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T19:12:49Z","timestamp":1670094769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-020-01575-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,3]]},"references-count":87,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["1575"],"URL":"https:\/\/doi.org\/10.1038\/s42003-020-01575-z","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,3]]},"assertion":[{"value":"19 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare the following competing interests: Henrik Ullum received an unrestricted research grant from Novartis. Cristian Erikstrup received an unrestricted research grant from Abbott. S\u00f8ren Brunak reports grants from Innovation Fund Denmark, grants from Novo Nordisk Foundation during the conduct of the study; and personal fees from Intomics A\/S and Proscion A\/S, outside the submitted work. John Danesh sits on the International Cardiovascular and Metabolic Advisory Board for Novartis (since 2010); the Steering Committee of UK Biobank (since 2011); the MRC International Advisory Group (ING) member, London (since 2013); the MRC High Throughput Science \u2018Omics Panel Member, London (since 2013); the Scientific Advisory Committee for Sanofi (since 2013); the International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis; and the Astra Zeneca Genomics Advisory Board (2018). Adam S. Butterworth has received grants outside of this work from AstraZeneca, Biogen, BioMarin, Bioverativ, Merck, and Novartis and personal fees from Novartis. For the authors who are affiliated with deCODE genetics\/Amgen, we declare competing financial interests as employees.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"156"}}