De novo discovery of traits co-occurring with chronic obstructive pulmonary disease

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.

An unbiasedde novonetwork analysis uncovering causal genes and the developmental intersection between autism and co-occurring traits

“…Potential co-occurring traits were identified using the Multimorbid3D pipeline (Golovina et al 2023;Zaied et al 2023) (https://github.com/Genome3d/multimorbid3D). The 576 autismassociated SNPs underwent a linkage disequilibrium analysis to determine those in LD (r 2 = 0.8, width = 5000 bp; supplementary table S2).…”

“…The copyright holder for this preprint this version posted April 26, 2023. ; https://doi.org/10. 1101 To investigate the interconnectivity of complex polygenic traits, network-based analyses have been previously used by our group (Golovina et al 2023). In this study, we identified causative and pleiotropic genes that are affected by SNPs associated with both autism and other traits within cortical gene regulatory networks (GRNs) at two different developmental stages.…”

Efficacy of auricular acupressure on lung function among chronic obstructive pulmonary disease: A meta‐analysis of randomised controlled trials

“…It was estimated that the global prevalence of COPD is 10.3% (Adeloye et al., 2022). More than 3.2 million people die from COPD annually, and it is the third leading cause of death worldwide (Golovina et al., 2022; Lu et al., 2022). With the development of medical technology, the survival rate of COPD patients is increasing year by year (Collaborators., 2016; Dong et al., 2021; Lash et al., 2011).…”

Identifying the genetic links between Parkinson’s disease and non-motor symptoms: novel insights into disease mechanisms

“…genetic risk, chromatin structure, protein interactions and phenotypes) to inform on the mechanistic interactions that impact on shared inherited genetic risk. We have developed a de novo analytical approach that uses Protein-Protein Interaction Networks (PPIN) to identify connections across these levels [14][15][16][17] . The use of tissue-speci c Gene Regulatory Networks (GRN) within this integrative approach identi es conditions/traits co-occurring with PD, and the genetic variation and biological pathway(s) that is responsible for the observed cooccurrence.…”

“…Here, we performed an unbiased, de novo analysis 14,15,17,18 integrating the Brain Cortex-speci c Gene Regulatory Network (BC-GRN), PPIN and GWAS data. We identify genes expressed in the brain cortex that are causally related to PD.…”