European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
Budu-Aggrey, Ashley; Kilanowski, Anna; Sobczyk, Maria K; Shringarpure, Suyash S; Mitchell, Ruth; 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 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 (2023-10-04)
Springer
04.10.2023
Budu-Aggrey, A., Kilanowski, A., Sobczyk, M.K. et al. European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation. Nat Commun 14, 6172 (2023). https://doi.org/10.1038/s41467-023-41180-2
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© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/.
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202312113609
https://urn.fi/URN:NBN:fi:oulu-202312113609
Tiivistelmä
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.
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.
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