PT  - JOURNAL ARTICLE
AU  - J. Smolonska
AU  - P. Zanen
AU  - H.J.M. Groen
AU  - A.E. Dijkstra
AU  - D.S. Postma
AU  - M. Oudkerk
AU  - B.J. de Hoop
AU  - B. van Ginneken
AU  - W. Mali
AU  - J.-W. Lammers
AU  - C. Wijmenga
AU  - H.M. Boezen
TI  - Genetic overlap of airway obstruction and emphysema
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - 1730
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/1730.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/1730.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Airway obstruction and emphysema are two features of chronic obstructive pulmonary disease (COPD). COPD patients can display one phenotype or both at one time. We used the Nelson cohort comprising ∼3000 individuals with lung function measurements and CT-scans to determine genes that contribute to both features. We performed genome-wide association studies on both sub-phenotypes. Airway obstruction was investigated in a case-control design (1030 cases with FEV1/FVC<0.7, 953 controls with FEV1/FVC>0.7 and FEV1 >90%pred, both groups being heavy-smokers with >20 pack-years, and 846 blood bank controls). Emphysema was investigated as a quantitative trait. To account for center-derived differences in these measurements we used 15th percentile (p15) of density distribution adjusted for air density in the trachea. p15 was analyzed using linear regression adjusting for age and pack-years smoking in 3047 subjects. To find overlap between these two sub-phenotypes we selected all SNPs with p<0.001 in each analysis, yielding a total of nine SNPs corresponding to four genes. When these genes were investigated in GeneMania they were enriched with an additional 9 genes directly interacting or co-expressed/co-localized with query genes and two of them point to a drug resistance pathway (GATHER p<0.0001, Bayes factor 6).This is an interesting approach that can help identifying a shared etiology of two distinct sub-phenotypes of a single complex disease.