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

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  • dc.contributor.author Budu-Aggrey, Ashley
  • dc.contributor.author Bustamante Pineda, Mariona
  • dc.contributor.author Standl, Marie
  • dc.date.accessioned 2024-01-16T07:10:55Z
  • dc.date.available 2024-01-16T07:10:55Z
  • dc.date.issued 2023
  • dc.description.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.
  • dc.description.sponsorship For this work, A.B.-A., S.J.B. and L.P. were funded by the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No. 821511 (BIOMAP). The J.U. receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. This publication reflects only the author’s view and the J.U. is not responsible for any use that may be made of the information it contains. A.B.A., M.K.S., J.L.M., and L.P. and work in a research unit funded by the UK Medical Research Council (MC_UU_00011/1 and MC_UU_00011/4). LP received funding from the British Skin Foundation (8010 Innovative Project) and the Academy of Medical Sciences Springboard Award, which is supported by the Wellcome Trust, The Government Department for Business, Energy and Industrial Strategy, the Global Challenges Research Fund and the British Heart Foundation [SBF003\1094]. S.J.B. holds a Wellcome Trust Senior Research Fellowship in Clinical Science [220875/Z/20/Z]. S.H. is supported by a Vera Davie Study and Research Sabbatical Bursary, NRF Thuthuka Grant (117721), NRF Competitive Support for Unrated Researcher (138072), MRC South Africa under a Self-initiated grant. M.S. has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 949906). Thanks to Sergi Sayols (developer of rrvgo), who provided additional code to alter the scatter plot produced by rrvgo to only display parent terms, and to Gibran Hemani (University of Bristol) who provided valuable guidance on the comparison of effects between ancestries. This publication is the work of the authors and LP will serve as guarantor for the contents of this paper. This work was carried out using the computational facilities of the Advanced Computing Research Centre, University of Bristol—http://www.bristol.ac.uk/acrc/. Individual cohort acknowledgements are in the Supplementary Methods.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Budu-Aggrey A, Kilanowski A, Sobczyk MK; 23andMe Research Team; Shringarpure SS, Mitchell R, et al. European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation. Nat Commun. 2023 Oct 4;14(1):6172. DOI: 10.1038/s41467-023-41180-2
  • dc.identifier.doi http://dx.doi.org/10.1038/s41467-023-41180-2
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/58728
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Commun. 2023 Oct 4;14(1):6172
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/949906
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/821511
  • dc.rights © The Author(s) 2023. 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/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Genome-wide association studies
  • dc.subject.keyword Skin diseases
  • dc.title European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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Articles (Barcelona Institute for Global Health (ISGlobal) – Campus Mar)
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