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Article Dans Une Revue Cell Genomics Année : 2023

Comprehensive epigenomic profiling reveals the extent of disease-specific chromatin states and informs target discovery in ankylosing spondylitis

Carla Jayne Cohen
Matteo L. Vecellio
Ping Zhang
  • Fonction : Auteur
Trevor J. Howe
  • Fonction : Auteur

Résumé

Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterized by enthesitis of the spine and sacroiliac joints. Genome-wide association studies (GWASs) have revealed more than 100 genetic associations whose functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls. We find that, while CD14+ monocytes and CD4+ and CD8+ T cells show disease-specific differences at the RNA level, epigenomic differences are only apparent upon multi-omics integration. The latter reveals enrichment at disease-associated loci in monocytes. We link putative functional SNPs to genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1, and show how disease-specific functional genomic data can be integrated with GWASs to enhance therapeutic target discovery. This study combines epigenetic and transcriptional analysis with GWASs to identify disease-relevant cell types and gene regulation of likely pathogenic relevance and prioritize drug targets.
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hal-04191701 , version 1 (21-09-2023)

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Andrew C. Brown, Carla Jayne Cohen, Olga Mielczarek, Gabriele Migliorini, Félicie Costantino, et al.. Comprehensive epigenomic profiling reveals the extent of disease-specific chromatin states and informs target discovery in ankylosing spondylitis. Cell Genomics, 2023, 3 (6), ⟨10.1016/j.xgen.2023.100306⟩. ⟨hal-04191701⟩
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