Splicing QTL mapping in stimulated macrophages associates low-usage splice junctions with immune-mediated disease risk

Omar El Garwany, Nikolaos I. Panousis, Andrew Knights, Natsuhiko Kumasaka, Maria Imaz, Lorena Boquete Vilarino, Anthi Tsingene, Alex Tokolyi, Cristina Cotobal Martin, Tobi Alegbe, Monika Krzak, Tim Raine, Alice Barnett, Celine Gomez, Daniel J. Gaffney () and Carl A. Anderson ()
Additional contact information
Omar El Garwany: Wellcome Genome Campus
Nikolaos I. Panousis: Wellcome Genome Campus
Andrew Knights: Wellcome Genome Campus
Natsuhiko Kumasaka: Wellcome Genome Campus
Maria Imaz: Wellcome Genome Campus
Lorena Boquete Vilarino: Wellcome Genome Campus
Anthi Tsingene: Wellcome Genome Campus
Alex Tokolyi: Wellcome Genome Campus
Cristina Cotobal Martin: Wellcome Genome Campus
Tobi Alegbe: Wellcome Genome Campus
Monika Krzak: Wellcome Genome Campus
Tim Raine: Cambridge University Teaching Hospitals
Alice Barnett: Wellcome Genome Campus
Celine Gomez: Wellcome Genome Campus
Daniel J. Gaffney: Wellcome Genome Campus
Carl A. Anderson: Wellcome Genome Campus

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract The majority of immune-mediated disease (IMD) risk loci are located in non-coding regions of the genome, making it difficult to decipher their functional effects in relevant physiological contexts. To assess the extent to which alternative splicing contributes to IMD risk, we mapped genetic variants associated with alternative splicing (splicing quantitative trait loci or sQTL) in macrophages exposed to a wide range of environmental stimuli. We found that genes involved in innate immune response pathways undergo extensive differential splicing in response to stimulation and detected significant sQTL effects for over 5734 genes across all stimulation conditions. We colocalised sQTL signals for over 700 genes with IMD-associated risk loci from 22 IMDs with high confidence (PP4 ≥ 0.75). Approximately half of the colocalisations implicate lowly-used splice junctions (mean usage ratio

Date: 2025
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61669-2 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:16:y:2025:i:1:d:10.1038_s41467-025-61669-2

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

DOI: 10.1038/s41467-025-61669-2

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 ().