PT  - JOURNAL ARTICLE
AU  - D.A. Van der Plaat
AU  - K. De Jong
AU  - J.M. Vonk
AU  - C.C. Van Diemen
AU  - C.M. Van Duijn
AU  - L. Lahousse
AU  - G.G. Brusselle
AU  - D.S. Postma
AU  - H.M. Boezen
TI  - Identification of novel genes related to airway obstruction in never-smokers
AID  - 10.1183/13993003.congress-2015.OA1459
DP  - 2015 Sep 01
TA  - European Respiratory Journal
PG  - OA1459
VI  - 46
IP  - suppl 59
4099  - http://erj.ersjournals.com/content/46/suppl_59/OA1459.short
4100  - http://erj.ersjournals.com/content/46/suppl_59/OA1459.full
SO  - Eur Respir J2015 Sep 01; 46
AB  - Background: Although a striking proportion (25-45%) of patients with chronic obstructive pulmonary disease (COPD) are never-smokers, most genetic susceptibility studies have not focussed on this group exclusively.Objective: This study aims to identify common genetic variants associated with airway obstruction in never-smokers by performing a genome-wide association (GWA) study on the ratio of FEV1 to FVC (FEV1/FVC).Methods: We used linear regression to analyse the association between 227,981 genotyped single nucleotide polymorphisms (SNPs) and the level of FEV1/FVC in 5,070 never-smokers of the LifeLines study. Results were verified in never-smokers of two other cohorts, namely the Vlagtwedde-Vlaardingen study (n = 432) and the Rotterdam study I (n = 408).Results: Seven top SNPs were associated with the level of FEV1/FVC (p-value < 1.2*10-5) in never-smokers of the LifeLines study and were verified in the two other cohorts. Although the SNPs did not reach genome-wide significance in the meta-analysis (p-value < 2.2*10-7) of the three cohorts, we observed similar directions and magnitudes of effects for four SNPs. We identified two novel SNPs, located in introns of AGAP1, which is involved in membrane trafficking and cytoskeleton dynamics, and PACSIN2 which plays a role in vesicle formation and transport. The other two SNPs are located nearby HHIP and in an intron of FAM13A, previously identified in GWA studies on COPD (in smokers).Discussion: In never-smokers, we found associations of airway obstruction with both novel genetic variants and with genetic variants previously identified in GWA studies on COPD. This could indicate that these genes play a role in the pathogenesis of non-smoking related COPD.