Genetics of chronic obstructive pulmonary disease

Area of Science:

• Pulmonary Medicine
• Genetics
• Environmental Health

Background:

• Chronic obstructive pulmonary disease (COPD) susceptibility is influenced by genetic and environmental factors.
• Severe alpha 1-antitrypsin (AAT) deficiency (protease inhibitor Z) is the only established genetic risk for COPD.
• Variability in lung function among individuals with severe AAT deficiency suggests the presence of genetic modifiers.

Purpose of the Study:

• To explore the genetic underpinnings of COPD susceptibility beyond severe AAT deficiency.
• To investigate genetic influences on lung function trajectories and COPD development.
• To address inconsistencies in previous candidate gene association studies for COPD.

Main Methods:

• Review of genetic association studies investigating candidate COPD gene loci.
• Analysis of linkage studies to identify genomic regions associated with COPD susceptibility.
• Discussion of potential reasons for conflicting results in association studies, including genetic heterogeneity and population stratification.

Main Results:

• Inconsistent results are common in candidate gene association studies for COPD.
• Severe AAT deficiency is the only confirmed genetic risk factor for COPD.
• Linkage analysis studies are emerging as a method to identify COPD susceptibility genes.

Conclusions:

• Genetic heterogeneity and population stratification may explain conflicting findings in COPD genetic association studies.
• Family-based designs and linkage analysis are recommended for future COPD genetic research.
• Identifying genetic modifiers is crucial for understanding COPD variability, even in severe AAT deficiency.