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BMC Gastroenterology
Published in: BMC Gastroenterology 1/2024

Open Access 01-12-2024 | Primary Sclerosing Cholangitis | Research

Investigating the shared genetic architecture between primary sclerosing cholangitis and inflammatory bowel diseases: a Mendelian randomization study

Authors: Xuan Dong, Li-Li Gong, Mei-Zhu Hong, Jin-Shui Pan

Published in: BMC Gastroenterology | Issue 1/2024

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Abstract

Background

Several studies have found that primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are closely associated. However, the direction and causality of their interactions remain unclear. Thus, this study employs Mendelian Randomization to explore whether there are causal associations of genetically predicted PSC with IBD.

Methods

Genetic variants associated with the genome-wide association study (GWAS) of PSC were used as instrumental variables. The statistics for IBD, including ulcerative colitis (UC), and Crohn’s disease (CD) were derived from GWAS. Then, five methods were used to estimate the effects of genetically predicted PSC on IBD, including MR Egger, Weighted median (WM), Inverse variance weighted (IVW), Simple mode, and Weighted mode. Last, we also evaluated the pleiotropic effects, heterogeneity, and a leave-one-out sensitivity analysis that drives causal associations to confirm the validity of the analysis.

Results

Genetically predicted PSC was significantly associated with an increased risk of UC, according to the study (odds ratio [OR] IVW= 1.0014, P<0.05). However, none of the MR methods found significant causal evidence of genetically predicted PSC in CD (All P>0.05). The sensitivity analysis results showed that the causal effect estimations of genetically predicted PSC on IBD were robust, and there was no horizontal pleiotropy or statistical heterogeneity.

Conclusions

Our study corroborated a causal association between genetically predicted PSC and UC but did not between genetically predicted PSC and CD. Then, we identification of shared SNPs for PSC and UC, including rs3184504, rs9858213, rs725613, rs10909839, and rs4147359. More animal experiments and clinical observational studies are required to further clarify the underlying mechanisms of PSC and IBD.
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Metadata
Title
Investigating the shared genetic architecture between primary sclerosing cholangitis and inflammatory bowel diseases: a Mendelian randomization study
Authors
Xuan Dong
Li-Li Gong
Mei-Zhu Hong
Jin-Shui Pan
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2024
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-024-03162-6

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