Journal article
An isoform quantitative trait locus in SBNO2 links genetic susceptibility to Crohn's disease with defective antimicrobial activity
- Abstract:
- Despite major advances in linking single genetic variants to single causal genes, the significance of genetic variation on transcript-level regulation of expression, transcript-specific functions, and relevance to human disease has been poorly investigated. Strawberry notch homolog 2 (SBNO2) is a candidate gene in a susceptibility locus with different variants associated with Crohn's disease and bone mineral density. The SBNO2 locus is also differentially methylated in Crohn's disease but the functional mechanisms are unknown. Here we show that the isoforms of SBNO2 are differentially regulated by lipopolysaccharide and IL-10. We identify Crohn's disease associated isoform quantitative trait loci that negatively regulate the expression of the noncanonical isoform 2 corresponding with the methylation signals at the isoform 2 promoter in IBD and CD. The two isoforms of SBNO2 drive differential gene networks with isoform 2 dominantly impacting antimicrobial activity in macrophages. Our data highlight the role of isoform quantitative trait loci to understand disease susceptibility and resolve underlying mechanisms of disease.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.7MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-024-47218-3
Authors
+ National Institute for Health Research
More from this funder
- Funder identifier:
- https://ror.org/0187kwz08
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 15
- Issue:
- 1
- Article number:
- 4529
- Place of publication:
- England
- Publication date:
- 2024-05-28
- Acceptance date:
- 2024-03-25
- DOI:
- EISSN:
-
2041-1723
- Pmid:
-
38806456
- Language:
-
English
- Keywords:
- Pubs id:
-
2002539
- Local pid:
-
pubs:2002539
- Deposit date:
-
2024-08-05
Terms of use
- Copyright holder:
- Aschenbrenner et al
- Copyright date:
- 2024
- Rights statement:
- © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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