title: Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Chronic bronchitis (CB) is one of the classic phenotypes of COPD. The aims of our study were to investigate genetic variants associated with COPD subjects with CB relative to smokers with normal spirometry, and to assess for genetic differences between subjects with CB and without CB within the COPD population.
  
  
  METHODS
  We analyzed data from current and former smokers from three cohorts: the COPDGene Study; GenKOLS (Bergen, Norway); and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). CB was defined as having a cough productive of phlegm on most days for at least 3 consecutive months per year for at least 2 consecutive years. CB COPD cases were defined as having both CB and at least moderate COPD based on spirometry. Our primary analysis used smokers with normal spirometry as controls; secondary analysis was performed using COPD subjects without CB as controls. Genotyping was performed on Illumina platforms; results were summarized using fixed-effect meta-analysis.
  
  
  RESULTS
  For CB COPD relative to smoking controls, we identified a new genome-wide significant locus on chromosome 11p15.5 (rs34391416, OR = 1.93, P = 4.99 × 10-8) as well as significant associations of known COPD SNPs within FAM13A. In addition, a GWAS of CB relative to those without CB within COPD subjects showed suggestive evidence for association on 1q23.3 (rs114931935, OR = 1.88, P = 4.99 × 10-7).
  
  
  CONCLUSIONS
  We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6). This study provides further evidence that genetic variants may contribute to phenotypic heterogeneity of COPD.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00608764, NCT00292552.
authors.forename: Jin Hwa
authors.initials: JH
authors.lastname: Lee
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cho
authors.forename: Craig P
authors.initials: CP
authors.lastname: Hersh
authors.forename: Merry-Lynn N
authors.initials: ML
authors.lastname: McDonald
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.forename: Per S
authors.initials: PS
authors.lastname: Bakke
authors.forename: Amund
authors.initials: A
authors.lastname: Gulsvik
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Comellas
authors.forename: Christine H
authors.initials: CH
authors.lastname: Wendt
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Victor
authors.initials: V
authors.lastname: Kim
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
mesh_terms: D000368:Aged; D029481:Bronchitis, Chronic / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics; D056426:Genetic Loci; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: C570078:FAM13A protein, human; D020690:GTPase-Activating Proteins; D005819:Genetic Markers