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.

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Epidemiological research indicates that chronic obstructive pulmonary disease (COPD) is a heterogeneous group of chronic lung conditions that are typically accompanied by cardiovascular disease, depression, lung cancer and other conditions. Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with COPD and the co-occuring conditions, suggesting common biological mechanisms underlying COPD and these co-occuring 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. Our results show that 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 underly these co-occuring 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.

We were unable to find any adverse consequences of use of IV iron when used to treat anemia in patients with AKI in regard to recovery of AKI or mortality even in patients with a diagnosis of sepsis. Consideration of preemptive use of IV iron in AKI with severe anemia is warranted to determine if this would reduce RBC transfusion.