title: Genome-wide association study of lung function decline in adults with and without asthma.
abstract: BACKGROUND
  Genome-wide association studies have identified determinants of chronic obstructive pulmonary disease, asthma, and lung function level; however, none have addressed decline in lung function.
  
  
  OBJECTIVE
  We conducted the first genome-wide association study on the age-related decrease in FEV(1) and its ratio to forced vital capacity (FVC) stratified a priori by asthma status.
  
  
  METHODS
  Discovery cohorts included adults of European ancestry (1,441 asthmatic and 2,677 nonasthmatic participants: the Epidemiological Study on the Genetics and Environment of Asthma, the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults, and the European Community Respiratory Health Survey). The associations of FEV(1) and FEV(1)/FVC ratio decrease with 2.5 million single nucleotide polymorphisms (SNPs) were estimated. Thirty loci were followed up by in silico replication (1,160 asthmatic and 10,858 nonasthmatic participants: Atherosclerosis Risk in Communities, the Framingham Heart Study, the British 1958 Birth Cohort, and the Dutch Asthma Study).
  
  
  RESULTS
  Main signals identified differed between asthmatic and nonasthmatic participants. None of the SNPs reached genome-wide significance. The association between the height-related gene DLEU7 and FEV(1) decrease suggested for nonasthmatic participants in the discovery phase was replicated (discovery, P = 4.8 × 10(-6); replication, P = .03), and additional sensitivity analyses point to a relation to growth. The top ranking signal, TUSC3, which is associated with FEV(1)/FVC ratio decrease in asthmatic participants (P = 5.3 × 10(-8)), did not replicate. SNPs previously associated with cross-sectional lung function were not prominently associated with decline.
  
  
  CONCLUSIONS
  Genetic heterogeneity of lung function might be extensive. Our results suggest that genetic determinants of longitudinal and cross-sectional lung function differ and vary by asthma status.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors.forename: Medea
authors.initials: M
authors.lastname: Imboden
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bouzigon
authors.forename: Ivan
authors.initials: I
authors.lastname: Curjuric
authors.forename: Adaikalavan
authors.initials: A
authors.lastname: Ramasamy
authors.forename: Ashish
authors.initials: A
authors.lastname: Kumar
authors.forename: Dana B
authors.initials: DB
authors.lastname: Hancock
authors.forename: Jemma B
authors.initials: JB
authors.lastname: Wilk
authors.forename: Judith M
authors.initials: JM
authors.lastname: Vonk
authors.forename: Gian A
authors.initials: GA
authors.lastname: Thun
authors.forename: Valerie
authors.initials: V
authors.lastname: Siroux
authors.forename: Rachel
authors.initials: R
authors.lastname: Nadif
authors.forename: Florent
authors.initials: F
authors.lastname: Monier
authors.forename: Juan R
authors.initials: JR
authors.lastname: Gonzalez
authors.forename: Matthias
authors.initials: M
authors.lastname: Wjst
authors.forename: Joachim
authors.initials: J
authors.lastname: Heinrich
authors.forename: Laura R
authors.initials: LR
authors.lastname: Loehr
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Koppelman
authors.forename: Stefano
authors.initials: S
authors.lastname: Guerra
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
authors.forename: Christian
authors.initials: C
authors.lastname: Schindler
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.forename: Francine
authors.initials: F
authors.lastname: Kauffmann
authors.forename: Debbie L
authors.initials: DL
authors.lastname: Jarvis
authors.forename: Florence
authors.initials: F
authors.lastname: Demenais
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Probst-Hensch
mesh_terms: D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D055106:Genome-Wide Association Study; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins; D020641:Polymorphism, Single Nucleotide; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014797:Vital Capacity; D055815:Young Adult
chemical_list: C482307:DLEU7 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins