title: Genetic variants associated with lung function: the long life family study.
abstract: BACKGROUND
  Reduced forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) are strong predictors of mortality and lung function is higher among individuals with exceptional longevity. However, genetic factors associated with lung function in individuals with exceptional longevity have not been identified.
  
  
  METHODS
  We conducted a genome wide association study (GWAS) to identify novel genetic variants associated with lung function in the Long Life Family Study (LLFS) (n = 3,899). Replication was performed using data from the CHARGE/SpiroMeta consortia. The association between SNPs and FEV1 and FEV1/FVC was analyzed using a linear mixed effects model adjusted for age, age2, sex, height, field center, ancestry principal components and kinship structure to adjust for family relationships separately for ever smokers and never smokers. In the linkage analysis, we used the residuals of the FEV1 and FEV1/FVC, adjusted for age, sex, height, ancestry principal components (PCs), smoking status, pack-years, and field center.
  
  
  RESULTS
  We identified nine SNPs in strong linkage disequilibrium in the CYP2U1 gene to be associated with FEV1 and a novel SNP (rs889574) associated with FEV1/FVC, none of which were replicated in the CHARGE/SpiroMeta consortia. Using linkage analysis, we identified a novel linkage peak in chromosome 2 at 219 cM for FEV1/FVC (LOD: 3.29) and confirmed a previously reported linkage peak in chromosome 6 at 28 cM (LOD: 3.33) for FEV1.
  
  
  CONCLUSIONS
  Future studies need to identify the rare genetic variants underlying the linkage peak in chromosome 6 for FEV1.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, 515 Delaware Street SE, 1-136 Moos Towers, Minneapolis 55455, MN, USA. thya0003@umn.edu.
authors.forename: Bharat
authors.initials: B
authors.lastname: Thyagarajan
authors.forename: Mary
authors.initials: M
authors.lastname: Wojczynski
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Minster
authors.forename: Jason
authors.initials: J
authors.lastname: Sanders
authors.forename: Sandra
authors.initials: S
authors.lastname: Barral
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
authors.forename: Anne
authors.initials: A
authors.lastname: Newman
mesh_terms: D000368:Aged; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation / Q000502:physiology*; D055106:Genome-Wide Association Study / Q000379:methods* / Q000639:trends; D006801:Humans; D008136:Longevity / Q000502:physiology*; D008168:Lung / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*