(BQ) Part 2 book “COPD - Heterogeneity and personalized treatment” has contents: Genetics of COPD, imaging heterogeneity of COPD, asthma-COPD overlap syndrome, the spectrum of pulmonary disease in COPD, pharmacologic management, and other contents. | Genetics of COPD 11 Woo Jin Kim Introduction History of Genetic Studies for COPD Although environmental factors, including cigarette smoking and biomass smoke exposure, are major risk factors of COPD, genetic risk factors are also important [1]. In addition, an interaction between genetics and environment is believed to drive the development of COPD. Pathways that play a role in COPD pathogenesis include the response to oxidative stress, the protease–antiprotease imbalance, cell death, and inflammation [2–5]. Genetic studies have been performed to identify genetic risk factors and to understand the pathogenesis of COPD. Family- based studies and candidate gene association studies have found associations for many genes and loci. However, alpha-1 antitrypsin deficiency caused by mutations in SERPINA1 is the only established genetically driven cause of COPD that has a potential intervention so far [6]. Future research is needed to characterize the effect of genetic variants, validate gene function in humans and model systems, and elucidate the genes’ transcriptional and post-transcriptional regulatory mechanisms [7]. Family studies have supported genetic factors to play an important role in the development of COPD [8]. Twin studies have reported heritability of lung function between 30 and 50% [9]. Recently, heritability of COPD was estimated 35–40% in population-based study [10]. Genome-wide linkage analysis using Boston early onset COPD identified several loci that were associated with lung function that is the most important phenotype of COPD [11]. Candidate gene strategies were used to test hypothesis of genetic associations with COPD. However, there were few genetic associations that were consistently significant, and this strategy has limitation in identifying novel mechanisms of COPD. . Kim Department of Internal Medicine and Environmental Health Center, Kangwon National University, Chuncheon, South Korea e-mail: pulmo2@ Genome-Wide
