Integrative Analysis of DNA Methylation and Gene Expression Data Identifies as a Key Regulator of COPD

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Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease. It is the fourth leading cause of death in the world and is expected to be the third by 2020. COPD is a heterogeneous and complex disease consisting of obstruction in the small airways, emphysema, and chronic bronchitis. COPD is generally caused by exposure to noxious particles or gases, most commonly from cigarette smoking. However, only 20–25% of smokers develop clinically significant airflow obstruction. Smoking is known to cause epigenetic changes in lung tissues. Thus, genetics, epigenetic, and their interaction with environmental factors play an important role in COPD pathogenesis and progression. Currently, there are no therapeutics that can reverse COPD progression. In order to identify new targets that may lead to the development of therapeutics for curing COPD, we developed a systematic approach to identify key regulators of COPD that integrates genome-wide DNA methylation, gene expression, and phenotype data in lung tissue from COPD and control samples. Our integrative analysis identified 126 key regulators of COPD. We identified EPAS1 as the only key regulator whose downstream genes significantly overlapped with multiple genes sets associated with COPD disease severity.

Vyšlo v časopise: Integrative Analysis of DNA Methylation and Gene Expression Data Identifies as a Key Regulator of COPD. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004898
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004898

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