LD matrices associated with publication "GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets"

dataset

posted on 2024-12-11, 11:19 authored by Nick DandNick Dand, Philip E. Stuart, Lam C. Tsoi, Michael A. Simpson, James T. Elder

Preprint: Dand N, Stuart PE, et al., GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets, medRxiv. 2023 Oct 5:2023.10.04.23296543. doi: 10.1101/2023.10.04.23296543. PMID: 37873414

Abstract: Psoriasis is a common, debilitating immune-mediated skin disease. Genetic studies have identified biological mechanisms of psoriasis risk, including those targeted by effective therapies. However, the genetic liability to psoriasis is not fully explained by variation at robustly identified risk loci. To refine the genetic map of psoriasis susceptibility we meta-analysed 18 GWAS comprising 36,466 cases and 458,078 controls and identified 109 distinct psoriasis susceptibility loci, including 46 that have not been previously reported. These include susceptibility variants at loci in which the therapeutic targets IL17RA and AHR are encoded, and deleterious coding variants supporting potential new drug targets (including in STAP2, CPVL and POU2F3). We conducted a transcriptome-wide association study to identify regulatory effects of psoriasis susceptibility variants and cross-referenced these against single cell expression profiles in psoriasis-affected skin, highlighting roles for the transcriptional regulation of haematopoietic cell development and epigenetic modulation of interferon signalling in psoriasis pathobiology.

This dataset: This study used a custom LD reference panel comprising six GWAS datasets. Individual level genotype data for the CASP GWAS, PsA GWAS, and Exomechip case-control studies are available on dbGaP (dbGaP: phs000019.v1.p1 [https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000019.v1.p1], phs000982.v1.p1 [http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000982.v1.p1], and phs001306.v1.p1 [http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001306.v1.p1]), and WTCCC2 genotype data are archived at the European Genome-Phenome Archive (study ID EGAS00000000108 [https://ega-archive.org/studies/EGAS00000000108]). Data sharing restrictions do not allow making genotype data publicly available for the remaining two case-control cohorts. However, LD matrices based on the full reference panel for all 109 susceptibility loci have been deposited in the King’s Open Research Data System.