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A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases
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A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases
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Journal Article
A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases
2025
Overview
Lung and gastrointestinal diseases often occur together, leading to more adverse health outcomes than when a disease of one of these systems occurs alone. However, the potential genetic mechanisms underlying lung-gastrointestinal comorbidities remain unclear. Here, we leverage lung and gastrointestinal trait data from individuals of European, East Asian and African ancestries, to perform a large-scale genetic cross trait analysis, followed by functional annotation and Mendelian randomization analysis to explore the genetic mechanisms involved in the development of lung-gastrointestinal comorbidities. Notably, we find significant genetic correlations between 27 trait pairs among the European population. The highest correlation is between chronic bronchitis and peptic ulcer disease. At the variant level, we identify 42 candidate pleiotropic genetic variants (3 of them previously uncharacterized) in 14 trait pairs by integrating cross-trait meta-analysis, fine-mapping and colocalization analyses. We also find 66 candidate pleiotropic genes, most of which were enriched in immune or inflammatory response-related activities. Causal inference approaches result in 4 potential lung-gastrointestinal associations. Introducing the gut microbiota as a variable establishes a relationship between the genus
Parasutterella
, gastro-oesophageal reflux disease and asthma. In summary, our findings highlight the genetic relationship between lung and gastrointestinal diseases, providing insights into the genetic mechanisms underlying the development of lung gastrointestinal comorbidities.
Lung and gastrointestinal diseases often occur together. Here, the authors present a multi-ancestry study showing the shared genetic architecture between lung and gastrointestinal diseases.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ East Asian People - genetics
/ Gastroesophageal Reflux - genetics
/ Gastrointestinal Diseases - epidemiology
/ Gastrointestinal Diseases - genetics
/ Gastrointestinal Microbiome - genetics
/ Genetic Predisposition to Disease
/ Genome-Wide Association Study
/ Humanities and Social Sciences
/ Humans
/ Lung Diseases - epidemiology
/ Lungs
/ Mendelian Randomization Analysis
/ Polymorphism, Single Nucleotide
/ Science
