Molecular Genetics of Chronic Obstructive Pulmonary Disease

Abstract

It is well recognized that while smoking is a significant environmental cause of chronic obstructive pulmonary disease (COPD), not all smokers will develop disease. Family studies show an increased risk to relatives of patients with COPD, and linkage analysis highlighted areas of the genome which appear to be associated with COPD and measures of lung function. This all suggests that there is a genetic contribution to COPD susceptibility and severity. A variety of candidate genes have been suggested over the years, many with conflicting results. This may represent population differences or spurious results caused by underpowered studies. Genome‐wide methods for gene identification have also been reported, either based on analysis of gene expression, or on genome‐wide assessment of variation. These studies have revealed novel genes which warrant further investigation.

Key Concepts

  • There is a genetic contribution to the susceptibility of developing chronic obstructive pulmonary disease.

  • Candidate gene studies in COPD often report conflicting results.

  • Genome‐wide association studies provide an unbiased method for identifying new genes involved in COPD.

  • Differences in gene‐expression may provide clues about other genes involved in COPD.

Keywords: polymorphism; SNP; genetic susceptibility; lung disease; smoking

Figure 1.

Common region on 15q25 identified in GWAS of lung cancer and COPD. Output was generated using the HapMap website (www.hapmap.org; International HapMap Consortium, ).

Figure 2.

Approaches for identifying genes involved in disease. Integration of genome‐wide association studies, candidate gene analysis, plus transcriptomic and proteomic investigations all provide supporting evidence for particular genes.

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Further Reading

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Yang IA and Francis SM (2009) Deconstructing COPD using genomic tools. Respirology (Carlton, Victoria) 14(3): 313–317.

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Chappell, Sally, and Kalsheker, Noor A(Apr 2010) Molecular Genetics of Chronic Obstructive Pulmonary Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022414]