Genetic variants associated with lung function: the long life family study

BACKGROUND: Reduced forced expiratory volume in 1 second (FEV(1)) and the ratio of FEV(1) 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. METHOD: 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 FEV(1) and FEV(1)/FVC was analyzed using a linear mixed effects model adjusted for age, age(2), 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 FEV(1) and FEV(1)/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 FEV(1) and a novel SNP (rs889574) associated with FEV(1)/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 FEV(1)/FVC (LOD: 3.29) and confirmed a previously reported linkage peak in chromosome 6 at 28 cM (LOD: 3.33) for FEV(1). CONCLUSION: Future studies need to identify the rare genetic variants underlying the linkage peak in chromosome 6 for FEV(1). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-014-0134-x) contains supplementary material, which is available to authorized users.