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European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

2023; Nature Portfolio; Volume: 14; Issue: 1 Linguagem: Inglês

10.1038/s41467-023-41180-2

2041-1723

Ashley Budu‐Aggrey, Anna Kilanowski, Maria Sobczyk, Suyash Shringarpure, Ruth E. Mitchell, Kadri Reis, Anu Reigo, Reedik Mägi, Mari Nelis, Nao Tanaka, Ben Brumpton, Laurent F. Thomas, Pol Solé-Navais, Christopher Flatley, Antonio Espuela‐Ortiz, Esther Herrera‐Luis, Jesus V. T. Lominchar, Jette Bork‐Jensen, Ingo Marenholz, Aleix Arnau‐Soler, Ayoung Jeong, Katherine A. Fawcett, Hansjörg Baurecht, Elke Rodríguez, Alexessander Couto Alves, Ashish Kumar, Patrick Sleiman, Xiao Chang, Carolina Medina‐Gómez, Chen Hu, Cheng‐Jian Xu, Cancan Qi, Sarah El‐Heis, Philip Titcombe, Elie Antoun, João Fadista, Carol A. Wang, Elisabeth Thiering, Baojun Wu, Sara Kress, Dilini M. Kothalawala, Latha Kadalayil, Jiasong Duan, Hongmei Zhang, Sabelo Hadebe, Thomas J. Hoffmann, Eric Jorgenson, Hélène Choquet, Neil Risch, Pål R. Njølstad, Ole A. Andreassen, Stefan Johansson, Catarina Almqvist, Tong Gong, Vilhelmina Ullemar, Robert Karlsson, Patrik K. E. Magnusson, Agnieszka Szwajda, Esteban G. Burchard, Jacob P. Thyssen, Torben Hansen, Line Lund Kårhus, Thomas Meinertz Dantoft, Alexander C.S.N. Jeanrenaud, Ahla Ghauri, Andreas Arnold, Georg Homuth, Susanne Lau, Markus M. Nöthen, Norbert Hübner, Medea Imboden, Alessia Visconti, Mario Falchi, Véronique Bataille, Pirro G. Hysi, Natalia Ballardini, Dorret I. Boomsma, Jouke‐Jan Hottenga, Martina Müller‐Nurasyid, Tarunveer S. Ahluwalia, Jakob Stokholm, Bo Chawes, Ann‐Marie Malby Schoos, Ana Esplugues, Mariona Bustamante, Benjamin A. Raby, Syed Hasan Arshad, Chris German, Tõnu Esko, Lili Milani, Andres Metspalu, Chikashi Terao, Katrina Abuabara, Mari Løset, Kristian Hveem, Bo Jacobsson, María Pino-Yanes, David P. Strachan, Niels Grarup, Allan Linneberg, Young‐Ae Lee, Nicole Probst‐Hensch, Stephan Weidinger, Marjo‐Riitta Järvelin, Erik Melén, Hákon Hákonarson, Alan D. Irvine, Deborah Jarvis, Tamar Nijsten, Liesbeth Duijts, Judith M. Vonk, Gerard H. Koppelmann, Keith M. Godfrey, Sheila J. Barton, Bjarke Feenstra, Craig E. Pennell, Peter D. Sly, Patrick G. Holt, L. Keoki Williams, Hans Bisgaard, Klaus Bønnelykke, John A. Curtin, Angela Simpson, Clare Murray, Tamara Schikowski, Supinda Bunyavanich, Scott T. Weiss, John W. Holloway, Josine L. Min, Sara Brown, Marie Standl, Lavinia Paternoster,

IL-33, ST2, and ILC Pathways

Abstract Atopic 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.