“From Genetics to Network Medicine in Chronic Obstructive Pulmonary Disease (COPD)”
Abstract: Large-scale genome-wide association studies (GWAS) in many thousands of COPD cases and control subjects have identified more than 80 genomic regions that contain COPD susceptibility genes. Fine mapping and molecular studies have implicated a functional genetic variant that regulates the Hedgehog Interacting Protein (HHIP) gene; ongoing studies using massively parallel reporter assays are being used to identify functional variants in other COPD GWAS loci. Rare variant studies based on whole exome DNA sequencing in families of severe, early-onset COPD subjects have identified multiple potential rare genetic variants for COPD susceptibility, and whole genome sequencing studies are currently being performed to identify rare noncoding genetic determinants of COPD. Functional studies of COPD GWAS genes using in vitro systems and animal models are implicating key biological pathways in COPD pathogenesis. Although genetic association studies have provided important insights into many complex diseases, most of the genetic variation remains unexplained. Single genetic variants are unlikely to explain complex diseases, because perturbations of biological networks, not isolated genes, confer disease risk. Network medicine applies network science and systems biology methods to Omics data in order to understand complex diseases. Correlation-based networks, gene regulatory networks, and protein-protein interaction networks provide complementary information regarding complex diseases like COPD.
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