AI Article Synopsis
- - Genome-wide association studies have pinpointed various genetic regions affecting lung function at a single point in time, but the specific genetic factors influencing the long-term decline in lung function remain unclear.
- - The study analyzed data from over 4,000 participants to assess the relationship between known genetic regions and changes in lung function over time, finding that while these regions had a strong impact on baseline lung function, they did not significantly affect lung function decline.
- - Though no new genetic variants were found to be strongly associated with lung decline, the heritable nature of this decline indicates there may still be undiscovered genetic factors influencing it in the future.
Article Abstract
Background: Genome-wide association studies have identified numerous genetic regions that influence cross-sectional lung function. Longitudinal decline in lung function also includes a heritable component but the genetic determinants have yet to be defined.
Objectives: We aimed to determine whether regions associated with cross-sectional lung function were also associated with longitudinal decline and to seek novel variants which influence decline.
Methods: We analysed genome-wide data from 4167 individuals from the Busselton Health Study cohort, who had undergone spirometry (12 695 observations across eight time points). A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV and FEV/FVC. Potential additional regions of interest were identified and followed up in two independent cohorts.
Results: The 26 regions previously associated with cross-sectional lung function jointly showed a strong effect on baseline lung function (p=4.44×10 for FEV/FVC) but no effect on longitudinal decline (p=0.160 for FEV/FVC). This was replicated in an independent cohort. 39 additional regions of interest (48 variants) were identified; these associations were not replicated in two further cohorts.
Conclusions: Previously identified genetic variants jointly have a strong effect on cross-sectional lung function in adults but little or no effect on the rate of decline of lung function. It is possible that they influence COPD risk through lung development. Although no genetic variants have yet been associated with lung function decline at stringent genome-wide significance, longitudinal change in lung function is heritable suggesting that there is scope for future discoveries.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520280 | PMC |
| http://dx.doi.org/10.1136/thoraxjnl-2016-208448 | DOI Listing |
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