Fine-mapping and molecular characterisation of primary sclerosing cholangitis genetic risk loci

Elizabeth C. Goode, Laura Fachal, Nikolaos Panousis, Loukas Moutsianas, Rebecca E. McIntyre, Benjamin Yu Hang Bai, Norihito Kawasaki, Alexandra Wittmann, Tim Raine, Simon M. Rushbrook and Carl A. Anderson ()
Additional contact information
Elizabeth C. Goode: Hinxton
Laura Fachal: Hinxton
Nikolaos Panousis: Hinxton
Loukas Moutsianas: Hinxton
Rebecca E. McIntyre: Hinxton
Benjamin Yu Hang Bai: Hinxton
Norihito Kawasaki: Quadrum Institute
Alexandra Wittmann: Quadrum Institute
Tim Raine: University of Cambridge
Simon M. Rushbrook: Norfolk and Norwich University Hospital
Carl A. Anderson: Hinxton

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Genome-wide association studies of primary sclerosing cholangitis have identified 23 susceptibility loci. The majority of these loci reside in non-coding regions of the genome and are thought to exert their effect by perturbing the regulation of nearby genes. Here, we aim to identify these genes to improve the biological understanding of primary sclerosing cholangitis, and nominate potential drug targets. We first build an eQTL map for six primary sclerosing cholangitis-relevant T-cell subsets obtained from the peripheral blood of primary sclerosing cholangitis and ulcerative colitis patients. These maps identify 10,459 unique eGenes, 87% of which are shared across all six primary sclerosing cholangitis T-cell types. We then search for colocalisations between primary sclerosing cholangitis loci and eQTLs and undertake Bayesian fine-mapping to identify disease-causing variants. In this work, colocalisation analyses nominate likely primary sclerosing cholangitis effector genes and biological mechanisms at five non-coding (UBASH3A, PRKD2, ETS2 and AP003774.1/CCDC88B) and one coding (SH2B3) primary sclerosing cholangitis loci. Through fine-mapping we identify likely causal variants for a third of all primary sclerosing cholangitis-associated loci, including two to single variant resolution.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53602-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53602-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53602-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().