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

Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterised by enthesitis of the spine and sacroiliac joints. Genome-wide association studies have revealed >100 genetic associations but their 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 report differential disease signatures for specific genomic regions from individual -omic modalities and multi-omic integration, showing enrichment at genetically associated loci and evidence for altered monocyte function in AS. We link putative functional SNPs with cognate genes using high-resolution Capture-C at 10 loci, including PTGER4 and ETS1. We also show how disease-specific functional genomic data can be integrated with GWAS evidence to enhance therapeutic target discovery. This study combines multiple epigenetic and transcriptional analysis with GWAS to identify cell types, candidate drug target genes and transcriptional regulation of likely pathogenic relevance.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001008758	This dataset consists of functional genomic data from 20 Ankylosing Spondylitis patients and 35 Healthy Controls taken from CD4+ T cells, CD8+ T cells and CD14 Monocytes. It contains 364 paired end fastq files consisting of 104 total RNA-seq samples and 116 ATAC samples, for ChIP there are 46 H3K4me3 samples, 46 H3K27ac samples and 3 H3K4me1 samples, along with 49 paired input samples. The samples were sequenced on Illumina HiSeq4000, Illumina NextSeq500 and Illumina NovaSeq 6000 platforms.	Illumina HiSeq 4000 Illumina NovaSeq 6000 NextSeq 500	364

Publications	Citations
Comprehensive epigenomic profiling reveals the extent of disease-specific chromatin states and informs target discovery in ankylosing spondylitis. Brown AC, Cohen CJ, Mielczarek O, Migliorini G, Costantino F, Allcock A, Davidson C, Elliott KS, Fang H, Lledó Lara A, Martin AC, Osgood JA, Sanniti A, Scozzafava G, Vecellio M, Zhang P, Black MH, Li S, Truong D, Molineros J, Howe T, Wordsworth BP, Bowness P, Knight JC. Cell Genom 3: 2023 100306	8

Publications

Citations

Comprehensive epigenomic profiling reveals the extent of disease-specific chromatin states and informs target discovery in ankylosing spondylitis.
Brown AC, Cohen CJ, Mielczarek O, Migliorini G, Costantino F, Allcock A, Davidson C, Elliott KS, Fang H, Lledó Lara A, Martin AC, Osgood JA, Sanniti A, Scozzafava G, Vecellio M, Zhang P, Black MH, Li S, Truong D, Molineros J, Howe T, Wordsworth BP, Bowness P, Knight JC. Cell Genom 3: 2023 100306