Integrative genomics of chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a complex disease with both environmental and genetic determinants, the most important of which is cigarette smoking. There is marked heterogeneity in the development of COPD among persons with similar cigarette smoking histories, which is likely partially explained by genetic variation. Genomic approaches such as genomewide association studies and gene expression studies have been used to discover genes and molecular pathways involved in COPD pathogenesis; however, these “first generation” omics studies have limitations. Integrative genomic studies are emerging which can combine genomic datasets to further examine the molecular underpinnings of COPD. Future research in COPD genetics will likely use network-based approaches to integrate multiple genomic data types in order to model the complex molecular interactions involved in COPD pathogenesis. This article reviews the genomic research to date and offers a vision for the future of integrative genomic research in COPD.

COPD subtypes identified by network-based clustering of blood gene expression

“…While certain processes were most enriched in specific disease subtypes, there was also notable overlap in processes across subtypes. Compared to previous blood expression studies in smokers with and without COPD, the role of inflammatory responses is consistent with previous findings [11]. Prior histologic studies of lung tissue from smokers with COPD demonstrate increased presence of multiple inflammatory cell sub-populations in emphysematous lungs [17,18] and various aspects of the role of innate and adaptive immunity in response to cigarette smoke have been demonstrated by multiple groups [19].…”

“…While COPD is defined by a ratio of <0.7 between the forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC ratio), the smoke-induced lung damage characteristic of COPD occurs across the full spectrum of smokers, including those who do not meet the spirometric criteria for COPD [9,10]. Gene expression studies in COPD have been recently reviewed, and while there is notable heterogeneity between studies, most studies in lung tissue and peripheral blood have identified enrichment of differentially expressed genes in inflammatory pathways related to immune regulation, specifically B-cell and T-cell development and differentiation [11–13]. …”

miRNA‐206 regulates human pulmonary microvascular endothelial cell apoptosis via targeting in chronic obstructive pulmonary disease

“…1 Multiple lines of evidence have suggested that a wide range of factors such as genetic susceptibility and environment are involved in the initiation and progression of COPD. 7,8 Among all these biomarkers, microRNAs (miRNAs) have emerged to be key biomarkers for the prognosis and diagnosis of patients with COPD. Previous studies demonstrated that various biomarkers and molecular pathways are involved in the pathogenesis of COPD.…”

Reduced DNA methylation of sphingosine‐1 phosphate receptor 5 in alveolar macrophages in COPD: A potential link to failed efferocytosis

“…Epigenetic modifications, such as histone modification, have been reported in COPD in several studies . For example, histone deacetylase (HDAC) activity has been reported to be decreased in alveolar macrophages in COPD .…”