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

Budu-Aggrey, A; Kilanowski, A; Sobczyk, MK; 23andMe Research Team, ; Shringarpure, SS; Mitchell, R; Reis, K; Reigo, A; Estonian Biobank Research Team, ; Mägi, R; et al. Budu-Aggrey, A; Kilanowski, A; Sobczyk, MK; 23andMe Research Team; Shringarpure, SS; Mitchell, R; Reis, K; Reigo, A; Estonian Biobank Research Team; Mägi, R; Nelis, M; Tanaka, N; Brumpton, BM; Thomas, LF; Sole-Navais, P; Flatley, C; Espuela-Ortiz, A; Herrera-Luis, E; Lominchar, JVT; Bork-Jensen, J; Marenholz, I; Arnau-Soler, A; Jeong, A; Fawcett, KA; Baurecht, H; Rodriguez, E; Alves, AC; Kumar, A; Sleiman, PM; Chang, X; Medina-Gomez, C; Hu, C; Xu, C-J; Qi, C; El-Heis, S; Titcombe, P; Antoun, E; Fadista, J; Wang, CA; Thiering, E; Wu, B; Kress, S; Kothalawala, DM; Kadalayil, L; Duan, J; Zhang, H; Hadebe, S; Hoffmann, T; Jorgenson, E; Choquet, H; Risch, N; Njølstad, P; Andreassen, OA; Johansson, S; Almqvist, C; Gong, T; Ullemar, V; Karlsson, R; Magnusson, PKE; Szwajda, A; Burchard, EG; Thyssen, JP; Hansen, T; Kårhus, LL; Dantoft, TM; Jeanrenaud, ACSN; Ghauri, A; Arnold, A; Homuth, G; Lau, S; Nöthen, MM; Hübner, N; Imboden, M; Visconti, A; Falchi, M; Bataille, V; Hysi, P; Ballardini, N; Boomsma, DI; Hottenga, JJ; Müller-Nurasyid, M; Ahluwalia, TS; Stokholm, J; Chawes, B; Schoos, A-MM; Esplugues, A; Bustamante, M; Raby, B; Arshad, S; German, C; Esko, T; Milani, LA; Metspalu, A; Terao, C; Abuabara, K; Løset, M; Hveem, K; Jacobsson, B; Pino-Yanes, M; Strachan, DP; Grarup, N; Linneberg, A; Lee, Y-A; Probst-Hensch, N; Weidinger, S; Jarvelin, M-R; Melén, E; Hakonarson, H; Irvine, AD; Jarvis, D; Nijsten, T; Duijts, L; Vonk, JM; Koppelmann, GH; Godfrey, KM; Barton, SJ; Feenstra, B; Pennell, CE; Sly, PD; Holt, PG; Williams, LK; Bisgaard, H; Bønnelykke, K; Curtin, J; Simpson, A; Murray, C; Schikowski, T; Bunyavanich, S; Weiss, ST; Holloway, JW; Min, JL; Brown, SJ; Standl, M; Paternoster, L (2023) European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation. Nat Commun, 14 (1). p. 6172. ISSN 2041-1723 https://doi.org/10.1038/s41467-023-41180-2
SGUL Authors: Strachan, David Peter

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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.

Item Type: Article
Additional Information: Open Access 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/. © The Author(s) 2023
Keywords: 23andMe Research Team, Estonian Biobank Research Team
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: Nat Commun
ISSN: 2041-1723
Language: eng
Dates:
DateEvent
4 October 2023Published
24 August 2023Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
MC_UU_00011/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_UU_00011/4Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
949906Horizon 2020http://dx.doi.org/10.13039/501100007601
8010 Innovative ProjectBritish Skin Foundationhttp://dx.doi.org/10.13039/501100000296
SBF003\1094British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
821511Innovative Medicines Initiativehttp://dx.doi.org/10.13039/501100010767
117721National Research Foundationhttp://dx.doi.org/10.13039/501100001321
138072National Research Foundationhttp://dx.doi.org/10.13039/501100001321
220875/Z/20/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 37794016
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/115762
Publisher's version: https://doi.org/10.1038/s41467-023-41180-2

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