Triangulating molecular evidence to prioritize candidate causal genes at established atopic dermatitis loci

Maria K Sobczyk-Barad, Tom G Richardson, Verena Zuber, Josine L Min, Tom R Gaunt, Lavinia Paternoster*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review


Genome-wide association studies for atopic dermatitis (AD) have identified 25 reproducible loci. We attempt to prioritize candidate causal genes at these loci using extensive molecular resources compiled into a bioinformatics pipeline.

We identified a list of 103 molecular resources for AD aetiology, including expression, protein and DNA methylation QTL datasets in skin or immune-relevant tissues which were tested for overlap with GWAS signals. This was combined with functional annotation using regulatory variant prediction, and features such as promoter-enhancer interactions, expression studies and variant fine-mapping. For each gene at each locus, we condensed the evidence into a prioritization score.

Across the investigated loci, we detected significant enrichment of genes with adaptive immune regulatory function and epidermal barrier formation among the top prioritized genes. At 8 loci, we were able to prioritize a single candidate gene (IL6R, ADO, PRR5L, IL7R, ETS1, INPP5D, MDM1, TRAF3). In addition, at 6 of the 25 loci, our analysis prioritizes less familiar candidates (SLC22A5, IL2RA, MDM1, DEXI, ADO, STMN3).

Our analysis provides support for previously implicated genes at several AD GWAS loci, as well as evidence for plausible additional candidates at others, which may represent potential targets for drug discovery.
Original languageEnglish
Article numberS0022-202X(21)01160-XDOI
Pages (from-to)1-35
Number of pages35
JournalJournal of Investigative Dermatology
Publication statusAccepted/In press - 24 Apr 2021


  • GWAS
  • genome-wide association study
  • eczema
  • atopic dermatitis
  • triangulation
  • eQTL

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