European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
Author:
Budu-Aggrey AshleyORCID, Kilanowski Anna, Sobczyk Maria K, Shringarpure Suyash S, Mitchell RuthORCID, Reis Kadri, Reigo Anu, Mägi Reedik, Nelis Mari, Tanaka Nao, Brumpton Ben M, Thomas Laurent F, Sole-Navais Pol, Flatley Christopher, Espuela-Ortiz Antonio, Herrera-Luis Esther, Lominchar Jesus VT, Bork-Jensen Jette, Marenholz Ingo, Arnau-Soler Aleix, Jeong Ayoung, Fawcett Katherine A, Baurecht Hansjorg, Rodriguez Elke, Alves Alexassander Couto, Kumar Ashish, Sleiman Patrick M, Chang Xiao, Medina-Gomez Carolina, Hu Chen, Xu Cheng-jianORCID, Qi Cancan, El-Heis Sarah, Titcombe Philip, Antoun Elie, Fadista João, Wang Carol A, Thiering Elisabeth, Xiao Shujie, Kress Sara, Kothalawala Dilini M, Kadalayil Latha, Duan Jiasong, Zhang Hongmei, Hoffmann Thomas, Jorgenson EricORCID, Choquet Hélène, Risch Neil, Njølstad Pål, Andreassen Ole AORCID, Johansson Stefan, Almqvist Catarina, Gong Tong, Ullemar Vilhelmina, Karlsson Robert, Magnusson Patrik KE, Szwajda Agnieszka, Burchard Esteban G, Thyssen Jacob P, Hansen Torben, Kårhus Line L, Dantoft Thomas M, Jeanrenaud Alexander C.S.N., Ghauri Ahla, Arnold Andreas, Homuth Georg, Lau Susanne, Nöthen Markus MORCID, Hübner Norbert, Imboden Medea, Visconti AlessiaORCID, Falchi Mario, Bataille Veronique, Hysi Pirro, Ballardini Natalia, Boomsma Dorret IORCID, Hottenga Jouke J, Müller-Nurasyid Martina, Ahluwalia Tarunveer SORCID, Stokholm Jakob, Chawes BoORCID, Schoos Ann-Marie M, Esplugues Ana, Bustamante Mariona, Raby Benjamin, Arshad Hasan, German Chris, Esko Tõnu, Milani Lili A, Metspalu Andres, Terao Chikashi, Abuabara Katrina, Løset Mari, Hveem Kristian, Jacobsson Bo, Pino-Yanes Maria, Strachan David P, Grarup Niels, Linneberg Allan, Lee Young-Ae, Probst-Hensch Nicole, Weidinger Stephan, Jarvelin Marjo-Riitta, Melén Erik, Hakonarson Hakon, Irvine Alan D, Jarvis Debbie L, Nijsten Tamar, Duijts Liesbeth, Vonk Judith M, Koppelmann Gerard H, Godfrey Keith M, Barton Sheila J, Feenstra BjarkeORCID, Pennell Craig E, Sly Peter D, Holt Patrick G, Williams Keoki L, Bisgaard HansORCID, Bønnelykke Klaus, Curtin John, Simpson Angela, Murray Clare, Schikowski Tamara, Bunyavanich Supinda, Weiss Scott TORCID, Holloway John W, Min Josine, Brown Sara J, Standl Marie, Paternoster Lavinia,
Abstract
AbstractAtopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies 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 and 15 additional loci in the multi-ancestry analysis (6 novel). All 81 variants replicated in a separate European analysis. Eleven variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African). While four variants appeared to be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL signals 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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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