Year: 2022
Type: article
Abstract: Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of chronic lung conditions. Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) associated with COPD and the co-occurring conditions, suggesting common biological mechanisms underlying COPD and these co-occurring conditions. To identify them, we have integrated information across different biological levels (i.e., genetic variants, lung-specific 3D genome structure, gene expression and protein-protein interactions) to build lung-specific gene regulatory and protein-protein interaction networks. We have queried these networks using disease-associated SNPs for COPD, unipolar depression and coronary artery disease. COPD-associated SNPs can control genes involved in the regulation of lung or pulmonary function, asthma, brain region volumes, cortical surface area, depressed affect, neuroticism, Parkinson's disease, white matter microstructure and smoking behaviour. We describe the regulatory connections, genes and biochemical pathways that underlay these co-occurring trait-SNP-gene associations. Collectively, our findings provide new avenues for the investigation of the underlying biology and diverse clinical presentations of COPD. In so doing, we identify a collection of genetic variants and genes that may aid COPD patient stratification and treatment.
Source: Life Science Alliance
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,500
Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, NIH Office of the Director, National Cancer Institute, National Institute of Neurological Disorders and Stroke, Common Fund
OpenAlex ID: W4313247714