European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
Authors: Budu-Aggrey Ashley , Kilanowski Anna , Sobczyk Maria K. ,   23andMe Research Team, Shringarpure Suyash S. , Mitchell Ruth , Reis Kadri , Reigo Anu ,   Estonian Biobank Research Team, 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 V. T. , Bork-Jensen Jette , Marenholz Ingo , Arnau-Soler Aleix , Jeong Ayoung , Fawcett Katherine A. , Baurecht Hansjorg , Rodriguez Elke , Alves Alexessander Couto , Kumar Ashish , Sleiman Patrick M. , Chang Xiao , Medina-Gomez Carolina , Hu Chen , Xu Cheng-jian , Qi Cancan , El-Heis Sarah , Titcombe Philip , Antoun Elie , Fadista João , Wang Carol A. , Thiering Elisabeth , Wu Baojun , Kress Sara , Kothalawala Dilini M. , Kadalayil Latha , Duan Jiasong , Zhang Hongmei , Hadebe Sabelo , Hoffmann Thomas , Jorgenson Eric , Choquet Hélène , Risch Neil , Njølstad Pål , Andreassen Ole A. , Johansson Stefan , Almqvist Catarina , Gong Tong , Ullemar Vilhelmina , Karlsson Robert , Magnusson Patrik K. E. , 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 M. , Hübner Norbert , Imboden Medea , Visconti Alessia , Falchi Mario , Bataille Veronique , Hysi Pirro , Ballardini Natalia , Boomsma Dorret I. , Hottenga Jouke J. , Müller-Nurasyid Martina , Ahluwalia Tarunveer S. , Stokholm Jakob , Chawes Bo , Schoos Ann-Marie M. , Esplugues Ana , Bustamante Mariona , Raby Benjamin , Arshad Syed , 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 Deborah , Nijsten Tamar , Duijts Liesbeth , Vonk Judith M. , Koppelmann Gerard H. , Godfrey Keith M. , Barton Sheila J. , Feenstra Bjarke , Pennell Craig E. , Sly Peter D. , Holt Patrick G. , Williams L. Keoki , Bisgaard Hans , Bønnelykke Klaus , Curtin John , Simpson Angela , Murray Clare , Schikowski Tamara , Bunyavanich Supinda , Weiss Scott T. , Holloway John W. , Min Josine L. , Brown Sara J. , Standl Marie , Paternoster Lavinia 
Published: October 2023

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.