recent applications

The role of genes and exposures in COPD prevalence and incidence, lung function and lung function decline

Chronic Obstructive Pulmonary Disease (COPD) is the third cause of death worldwide. Its prevalence will increase in the forthcoming decades, resulting in an ongoing economical, societal and personal burden. Research on the origins of COPD has focused almost exclusively on cigarette smoking, and consequently, genetic susceptibility studies mainly addressed the origins of COPD in response to smoking. However, a striking 25-45% of COPD cases occurs in subjects who never smoked, being 53-84 million COPD patients worldwide. COPD in non-smokers thus is a major and increasing global health problem.

Our earlier studies on genetics of COPD have shown convincingly that specific genes are associated with COPD completely independent of smoking, extending the genetic susceptibility paradigm beyond cigarette smoke exposure and suggesting a role for COPD susceptibility genes in relation to other exposures. Our recent studies focussed specifically on the role of common genetic variants in non-smoking related COPD and the role of gene-by-exposure interactions underlying (non-smoking related) COPD. Numerous papers on this research theme were published already using the data of the first Lifelines visit. We have identified a large number of susceptibility genes for COPD per se, as well as susceptibility genes for COPD in the context of exposures other than cigarette smoking (being environmental tobacco smoke, job elated exposure and air pollution).  

The results of our genome wide association studies (GWAS) and genome wide interaction studies (GWIS) were based on cross-sectional analyses of the first visit of Lifelines. This means that we usually defined COPD based on presence of airway obstruction (ie. FEV1/FVC <0.70 or FEV1/FVC<lower limit of normal). This does not do justice to the fact that present COPD can be the results of different courses towards its onset, meaning that throughout adult life different paths can lead to the development of COPD. For example submaximal attained lung function level at young adult age as well as accelerated decline in lung function at adult age, or combinations of both, can lead to COPD. In these different paths leading to COPD, specific genes and environmental exposures may play a role and the effects of gene-by-environment interactions might be different in specific phases of life  (life course epidemiology). This is the rationale to study the role of genes and exposures in COPD prevalence and incidence, lung function and lung function decline.

New venues in COPD prevention focussing on genetic susceptibility for other exposures than cigarette smoking will bring our knowledge on the origins of COPD to the next level.

year of approval



  • University Medical Center Groningen

primary applicant

  • Boezen, HM