A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases

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.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2025-03-28
DOI
https://doi.org/10.1038/s41467-025-58248-w
Citations
14
Primary Topic
Cancer-related molecular mechanisms research
Type
article
Field-Weighted Citation Impact
13.11

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases

Hongbing Shen, Yaqian Wu, Hongxia Ma, Hongyang Xu et al.
14 citations
Nature Communications
Cancer-related molecular mechanisms research
13.11
article

A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases

Hongbing Shen, Yaqian Wu, Hongxia Ma, Hongyang Xu, Sipeng Shen, Zewei Zhou, Ruyang Zhang, Guangfu Jin, Fang Shao, Yingdan Tang, Theis Lange, Mengyi Lu, Yongmei Yin, Dongfang You, David C. Christiani, Feng Chen, Sisi Liu, Liya Liu, Yang Zhao
article en
14 citations

Abstract

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.

Nature CommunicationsVol. 16(1)
Ningbo University (CN), University of Copenhagen (DK), Harvard University (US), Ministry of Education (KR), Jiangsu Cancer Hospital (CN), Jiangsu Province Hospital (CN), Wuxi People's Hospital (CN), Nanjing Medical University (CN)
GlaxoSmithKline, Wellcome Trust, Cancer Research UK, British Heart Foundation, National Natural Science Foundation of China, Government of Jiangsu Province, Ningbo University, Nanjing Medical University, Faculty of Health and Medical Sciences, University of Western Australia, Priority Academic Program Development of Jiangsu Higher Education Institutions, Medical Research Council, Det Sundhedsvidenskabelige Fakultet, Københavns Universitet
Zero hunger
Openalex Percentile: Top 1%
Cancer-related molecular mechanisms research
13.11
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.