title: No convincing association between genetic markers and respiratory symptoms: results of a GWA study.
abstract: Respiratory symptoms are associated with accelerated lung function decline, and increased hospitalization and mortality rates in the general population. Although several environmental risk factors for respiratory symptoms are known, knowledge on genetic risk factors is lacking. We aim to identify genetic variants associated with respiratory symptoms by genome-wide association (GWA) analyses.
  
  
  
  We conducted the first GWA study on cough, dyspnea and phlegm among 7,976 participants in the LifeLines I cohort and used the LifeLines II cohort (n = 5,260) and the Vlagtwedde-Vlaardingen cohort (n = 1,529) for replication.
  
  
  
  We identified 50 SNPs that were assessed for replication. Rs16918212, located in the alpha-2-macroglobulin pseudogene 1 (A2MP1), was associated with cough in both the identification (odds ratio (OR) = 0.72, p = 5.41 × 10-5) and the meta-analyzed replication cohorts (OR = 0.83, p = 0.033). No other significant replicated associations were found.
  
  
  
  Given that only 1 out of 50 SNPs showed significant replication (i.e. 2%) we conclude that we did not find a convincing association between genetic markers and respiratory symptoms. Since, environmental exposures are important risk factors for respiratory symptoms, the next step is to perform a genome-wide interaction (GWI) study to identify genetic susceptibility loci for respiratory symptoms in interaction with known harmful environmental exposures.
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, 1 Hanzeplein, Groningen, 9700RB, The Netherlands.|Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, 1 Hanzeplein, Groningen, 9700RB, The Netherlands.|Laboratory of Environmental Medicine and Developmental Toxicology, and Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, 1 Hanzeplein, Groningen, 9700RB, The Netherlands.|Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, 1 Hanzeplein, Groningen, 9700RB, The Netherlands.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Vonk
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, 1 Hanzeplein, Groningen, 9700RB, The Netherlands.|Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, 1 Hanzeplein, Groningen, 9700RB, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: de Jong
authors.affiliation: Laboratory of Environmental Medicine and Developmental Toxicology, and Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, China.
authors.forename: Xijin
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Guangzhou Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, 510632, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Huo
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, 1 Hanzeplein, Groningen, 9700RB, The Netherlands. h.m.boezen@umcg.nl.|Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, 1 Hanzeplein, Groningen, 9700RB, The Netherlands. h.m.boezen@umcg.nl.
authors.forename: H Marike
authors.identifier: 0000-0002-4320-1481
authors.initials: HM
authors.lastname: Boezen
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence; D012120:Respiration Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors; D017678:Sex Distribution; D055815:Young Adult
chemical_list: D005819:Genetic Markers
keywords: GWAS; General population; Genetic; Respiratory symptoms; cohorts