Abstract
BackgroundReduced 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.MethodWe 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.ResultsWe 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.ConclusionFuture studies need to identify the rare genetic variants underlying the linkage peak in chromosome 6 for FEV1.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0134-x) contains supplementary material, which is available to authorized users.
Highlights
Pulmonary function, as determined by spirometry, indicates the physiological state of the airways and lung
We identified nine SNPs in strong linkage disequilibrium in the CYP2U1 gene to be associated with forced expiratory volume in 1 second (FEV1) and a novel SNP associated with FEV1/forced vital capacity (FVC), none of which were replicated in the CHARGE/SpiroMeta consortia
We have previously shown that the prevalence of self-reported chronic obstructive pulmonary disease (COPD) was 3 times lower in the Long Life Family Study (LLFS) as compared to the other aged cohorts [12] suggesting that LLFS participants, who were selected for exceptional familial longevity, may have better lung function as compared to the general population
Summary
As determined by spirometry, indicates the physiological state of the airways and lung. Pulmonary function measures such as forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of the two measures (FEV1/FVC) are used to diagnose chronic obstructive pulmonary disease (COPD) and assist in the diagnosis of asthma, which are major causes of death and morbidity worldwide [1]. 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. Genetic factors associated with lung function in individuals with exceptional longevity have not been identified
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