LAUSR

Chronic obstructive pulmonary disease (COPD) is a complex genetic disorder, strongly associated with smoking. However, 25-45% of the individuals who develop COPD have never been exposed to (environmental) smoking. We hypothesize that these individuals have a strong genetic susceptibility for COPD with rare, pathogenic genetic variants underlying its development. We studied 36 individuals from the prospective Dutch Lifelines cohort with COPD (LLN of FEV1/FVC In total, we found 7,638 unique predicted pathogenic genetic variants in the 36 selected individuals. All 36 individuals carry at least 1 variant (range 1-7) in the top-100 prioritized genes in the COPD network. GeneNetwork pathway analysis revealed that 56 of the prioritized genes were significantly enriched for biological processes involved in cilium functioning. Our results suggest that rare pathogenic variants in ciliary genes underlie non-smoking related COPD and their role in a mono- or oligogenic form of COPD should be further investigated.