Abstract
Asthma and chronic obstructive pulmonary disease (COPD) are major worldwide health problems. Pulmonary function testing is a useful diagnostic tool for these diseases, and is known to be influenced by genetic and environmental factors. Previous studies have demonstrated that a substantial proportion of the variation in pulmonary function phenotypes can be explained by familial relationships. The availability of whole-genome single nucleotide polymorphism (SNP) data enables us to further evaluate the extent to which genetic factors account for variation in pulmonary function and to compare pedigree- to SNP-based estimates of heritability. Here, we employ methods developed in the animal breeding field to estimate the heritability of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of these two measures (FEV1/FVC) among subjects in the Framingham Heart Study dataset. We compare heritability estimates based on pedigree-based relationships to those based on genome-wide SNPs. We find that, in a family-based study, estimates of heritability using SNP data are nearly identical to estimates based on pedigree information, and range from 0.50 for FEV1 to 0.66 for FEV1/FVC. Therefore, we conclude that genetic factors account for a sizable proportion of inter-individual differences in pulmonary function, and that estimates of heritability based on SNP data are nearly identical to estimates based on pedigree data. Finally, our findings suggest a higher heritability for FEV1/FVC compared to either FEV1 or FVC.
Highlights
Airway diseases are a major health burden, and one of the leading causes of death in the United States and worldwide (Lopez et al, 2006)
We find a negative association between age and FEV1 and forced vital capacity (FVC), suggesting a significant difference between males and females, with males having higher FEV1 and FVC, and earlier cohorts having lower FEV1 and FVC
For FEV1/FVC, we find that females have a higher mean value than males (p < 5 × 10−14)
Summary
Airway diseases are a major health burden, and one of the leading causes of death in the United States and worldwide (Lopez et al, 2006). The heritability of pulmonary function, defined as the proportion of phenotypic variation that can be accounted for by genetic variation, has been estimated using twin and family studies. Estimates range from approximately 40 to 55% (Redline et al, 1989; Givelber et al, 1998; Xu et al, 1999; Wilk et al, 2000). These studies suggest that genetic factors explain a substantial portion of inter-individual variation in pulmonary function. Heritability estimates using SNP-based methods, as opposed to pedigreebased methods, may allow for the accounting of variation introduced by chromosomal segregation. Pedigree-based methods may capture more common environmental factors than captured by genetic markers
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