| Title: | Triangulating Molecular Evidence to Prioritize Candidate Causal Genes at Established Atopic Dermatitis Loci |
| Journal: | Journal of Investigative Dermatology |
| Published: | 24 Apr 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33901562/ |
| DOI: | https://doi.org/10.1016/j.jid.2021.03.027 |
| URL: | http://www.jidonline.org/article/S0022202X2101160X/pdf |
| Citations: | 14 (9 in last 2 years) as of 8 Aug 2024 |
Publication 9673
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Abstract
GWASs for atopic dermatitis have identified 25 reproducible loci. We attempt to prioritize the candidate causal genes at these loci using extensive molecular resources compiled into a bioinformatics pipeline. We identified a list of 103 molecular resources for atopic dermatitis etiology, including expression, protein, and DNA methylation quantitative trait loci datasets in the 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 eight 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 atopic dermatitis GWAS loci as well as evidence for plausible additional candidates at others, which may represent potential targets for drug discovery.</p>
7 Authors
- Maria K. Sobczyk
- Tom G. Richardson
- Verena Zuber
- Josine L. Min
- Tom R. Gaunt
- Lavinia Paternoster
- BIOS Consortium eQTLGen Consortium
1 Application
| Application ID | Title |
|---|---|
| 10074 | Investigation of the genetic burden of eczema and the genetic overlap between eczema and related conditions |
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