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Respiratory Research
Published in: Respiratory Research 1/2023

Open Access 01-12-2023 | Research

Genetic and observational associations of lung function with gastrointestinal tract diseases: pleiotropic and mendelian randomization analysis

Authors: Minghui Jiang, Xingjie Hao, Yi Jiang, Si Li, Chaolong Wang, Shanshan Cheng

Published in: Respiratory Research | Issue 1/2023

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Abstract

Background

The two-way communications along the gut-lung axis influence the immune function in both gut and lung. However, the shared genetic characteristics of lung function with gastrointestinal tract (GIT) diseases remain to be investigated.

Methods

We first investigated the genetic correlations between three lung function traits and four GIT diseases. Second, we illustrated the genetic overlap by genome-wide pleiotropic analysis (PLACO) and further pinpointed the relevant tissue and cell types by partitioning heritability. Furthermore, we proposed pleiotropic genes as potential drug targets by drug database mining. Finally, we evaluated the causal relationships by epidemiologic observational study and Mendelian randomization (MR) analysis.

Results

We found lung function and GIT diseases were genetically correlated. We identified 258 pleiotropic loci, which were enriched in gut- and lung-specific regions marked by H3K4me1. Among these, 16 pleiotropic genes were targets of drugs, such as tofacitinib and baricitinib targeting TYK2 for the treatment of ulcer colitis and COVID-19, respectively. We identified a missense variant in TYK2, exhibiting a shared causal effect on FEV1/FVC and inflammatory bowel disease (rs12720356, PPLACO=1.38 × 10− 8). These findings suggested TYK2 as a promising drug target. Although the epidemiologic observational study suggested the protective role of lung function in the development of GIT diseases, no causalities were found by MR analysis.

Conclusions

Our study suggested the shared genetic characteristics between lung function and GIT diseases. The pleiotropic variants could exert their effects by modulating gene expression marked by histone modifications. Finally, we highlighted the potential of pleiotropic analyses in drug repurposing.
Appendix
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Metadata
Title
Genetic and observational associations of lung function with gastrointestinal tract diseases: pleiotropic and mendelian randomization analysis
Authors
Minghui Jiang
Xingjie Hao
Yi Jiang
Si Li
Chaolong Wang
Shanshan Cheng
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2023
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-023-02621-0

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