Exome sequencing and genotyping identify a rare variant in NLRP7 gene associated with ulcerative colitis.
Katrina de Lange,
Jeffrey C Barrett,
John C Mansfield,
Jeremy D. Sanderson,
Michael A. Simpson,
Christopher G. Mathew,
Natalie J. Prescott
Posted 29 Aug 2017
bioRxiv DOI: 10.1101/182113 (published DOI: 10.1093/ecco-jcc/jjx157)
Posted 29 Aug 2017
Background and aims: Although genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) have identified a large number of common disease susceptibility alleles for both Crohn's disease (CD) and ulcerative colitis (UC), a substantial fraction of IBD heritability remains unexplained, suggesting that rare coding genetic variants may also have a role in pathogenesis. We used high-throughput sequencing in families with multiple cases of IBD, followed by genotyping of cases and controls, to investigate whether rare protein altering genetic variants are associated with susceptibility to IBD. Methods: Whole exome sequencing was carried out in 10 families in which 3 or more individuals were affected with IBD. A stepwise filtering approach was applied to exome variants to identify potential causal variants. Follow-up genotyping was performed in 6,025 IBD cases (2,948 CD; 3,077 UC) and 7,238 controls. Results: Our exome variant analysis revealed coding variants in the NLRP7 gene that were present in affected individuals in two distinct families. Genotyping of the two variants, p.S361L and p.R801H, in IBD cases and controls showed that the p.S361L variant was significantly associated with an increased risk of ulcerative colitis (odds ratio 4.79, p=0.0039) and IBD (odds ratio 3.17, p=0.037). A combined analysis of both variants showed suggestive association with an increased risk of IBD (odds ratio 2.77, p=0.018). Conclusions: The results suggest that NLRP7 signalling and inflammasome formation may be a significant component in the pathogenesis of IBD.
- Downloaded 278 times
- Download rankings, all-time:
- Site-wide: 53,493 out of 84,910
- In genetics: 3,058 out of 4,455
- Year to date:
- Site-wide: 72,862 out of 84,910
- Since beginning of last month:
- Site-wide: 76,876 out of 84,910
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!