European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
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Published:2023-10-04
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Budu-Aggrey AshleyORCID, Kilanowski AnnaORCID, Sobczyk Maria K.ORCID, Shringarpure Suyash S.ORCID, Mitchell RuthORCID, Reis KadriORCID, Reigo Anu, Mägi ReedikORCID, Nelis Mari, Tanaka NaoORCID, Brumpton Ben M.ORCID, Thomas Laurent F.ORCID, Sole-Navais PolORCID, Flatley Christopher, Espuela-Ortiz AntonioORCID, Herrera-Luis EstherORCID, Lominchar Jesus V. T., Bork-Jensen Jette, Marenholz Ingo, Arnau-Soler AleixORCID, Jeong AyoungORCID, Fawcett Katherine A.ORCID, Baurecht Hansjorg, Rodriguez ElkeORCID, Alves Alexessander CoutoORCID, Kumar Ashish, Sleiman Patrick M., Chang Xiao, Medina-Gomez CarolinaORCID, Hu Chen, Xu Cheng-jianORCID, Qi Cancan, El-Heis Sarah, Titcombe Philip, Antoun Elie, Fadista João, Wang Carol A.ORCID, Thiering Elisabeth, Wu Baojun, Kress SaraORCID, Kothalawala Dilini M., Kadalayil Latha, Duan Jiasong, Zhang HongmeiORCID, Hadebe Sabelo, Hoffmann ThomasORCID, Jorgenson Eric, Choquet HélèneORCID, Risch Neil, Njølstad PålORCID, Andreassen Ole A.ORCID, Johansson StefanORCID, Almqvist CatarinaORCID, Gong Tong, Ullemar Vilhelmina, Karlsson RobertORCID, Magnusson Patrik K. E.ORCID, Szwajda Agnieszka, Burchard Esteban G.ORCID, Thyssen Jacob P., Hansen TorbenORCID, Kårhus Line L., Dantoft Thomas M., Jeanrenaud Alexander C.S.N., Ghauri AhlaORCID, Arnold Andreas, Homuth GeorgORCID, Lau Susanne, Nöthen Markus M.ORCID, Hübner NorbertORCID, Imboden Medea, Visconti AlessiaORCID, Falchi MarioORCID, Bataille Veronique, Hysi PirroORCID, Ballardini Natalia, Boomsma Dorret I.ORCID, Hottenga Jouke J.ORCID, Müller-Nurasyid Martina, Ahluwalia Tarunveer S.ORCID, Stokholm JakobORCID, Chawes BoORCID, Schoos Ann-Marie M.ORCID, Esplugues Ana, Bustamante MarionaORCID, Raby Benjamin, Arshad Syed, German Chris, Esko Tõnu, Milani Lili A.ORCID, Metspalu AndresORCID, Terao ChikashiORCID, Abuabara Katrina, Løset MariORCID, Hveem Kristian, Jacobsson BoORCID, Pino-Yanes MariaORCID, Strachan David P.ORCID, Grarup NielsORCID, Linneberg AllanORCID, Lee Young-AeORCID, Probst-Hensch Nicole, Weidinger StephanORCID, Jarvelin Marjo-RiittaORCID, Melén ErikORCID, Hakonarson HakonORCID, Irvine Alan D.ORCID, Jarvis Deborah, Nijsten TamarORCID, Duijts Liesbeth, Vonk Judith M.ORCID, Koppelmann Gerard H.ORCID, Godfrey Keith M.ORCID, Barton Sheila J., Feenstra BjarkeORCID, Pennell Craig E.ORCID, Sly Peter D.ORCID, Holt Patrick G.ORCID, Williams L. Keoki, Bisgaard Hans, Bønnelykke KlausORCID, Curtin John, Simpson Angela, Murray ClareORCID, Schikowski Tamara, Bunyavanich SupindaORCID, Weiss Scott T., Holloway John W.ORCID, Min Josine L.ORCID, Brown Sara J., Standl MarieORCID, Paternoster LaviniaORCID, ,
Abstract
AbstractAtopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.
Funder
RCUK | Medical Research Council British Skin Foundation British Heart Foundation Academy of Medical Sciences Springboard Award, supported by the Wellcome Trust. The Government Department for Business, Energy and Industrial Strategy. The Global Challenges Research Fund Innovative Medicines Initiative National Research Foundation South African Medical Research Council Wellcome Trust
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference93 articles.
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