Genetic variants and lung function decline in the LifeLines cohort study

Introduction: Genome wide association studies (GWAS) have identified genetic variants associated with the presence of airway obstruction and COPD. These cross-sectional studies did not do justice to the fact that different paths can lead to COPD development. One path is accelerated lung function decline in adulthood, which may be influenced by genetic make-up and smoking. In this study, we aimed to identify genetic variants and gene-by-smoking interactions with lung function decline in the general population based LifeLines cohort study. Methods: We performed a GWAS on FEV1 decline after age 30 in 8,274 Lifelines subjects. Annual FEV1 decline was defined over 4.5 years of follow up. The analysis was adjusted for age, gender, height and smoking status at baseline. Additionally, a SNP-by-smoking interaction study (GWIS) was performed, with similar adjustments. Results: We found 73 variants in 15 genetic loci significantly associated with FEV1 decline (p Conclusion: We identified novel genetic variants associated with FEV1 decline in a large homogeneous cohort. Investigation of the gene-by-smoking interaction resulted in the identification of other novel genetic variants. All variants have not been identified in previous studies on FEV1 decline, indicating that this phenotype is very heterogeneous.