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

23andMe Research Team, Ashley Budu-Aggrey, Anna Kilanowski, Maria K Sobczyk, Suyash S Shringarpure, Ruth Mitchell, Kadri Reis, Anu Reigo, Reedik Mägi, Mari Nelis, Nao Tanaka, Ben M Brumpton, Laurent F Thomas, Pol Sole-Navais, Christopher Flatley, Antonio Espuela-Ortiz, Esther Herrera-Luis, Jesus V T Lominchar, Jette Bork-Jensen, Ingo MarenholzAleix Arnau-Soler, Ayoung Jeong, Katherine A Fawcett, Hansjorg Baurecht, Elke Rodriguez, Alexessander Couto Alves, Ashish Kumar, Patrick M Sleiman, Xiao Chang, Carolina Medina-Gomez, 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 Hoffmann, Eric Jorgenson, Hélène Choquet, Judith M Vonk, Scott T Weiss, Marie Standl, Lavinia Paternoster*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Article number6172
Number of pages18
JournalNature Communications
Volume14
DOIs
Publication statusPublished - 4-Oct-2023

Keywords

  • Humans
  • Genome-Wide Association Study
  • Dermatitis, Atopic/genetics
  • Genetic Predisposition to Disease/genetics
  • Hispanic or Latino/genetics
  • Black People
  • Polymorphism, Single Nucleotide

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