A genetic risk score associated with chronic obstructive pulmonary disease susceptibility and lung structure on computed tomography
American Journal of Respiratory and Critical Care Medicine Sep 18, 2019
Oelsner EC, Ortega VE, Smith BM, et al. - Researchers used data from a US general population–based cohort ie, MESA Lung (Multi-Ethnic Study of Atherosclerosis Lung Study), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), to describe links between a genetic risk score (GRS) related to chronic obstructive pulmonary disease (COPD) susceptibility and lung structure on computed tomography (CT). From 83 SNPs previously related to lung function, a weighted GRS was calculated. Using full-lung CT, lung density, spatially matched airway dimensions, and airway counts were evaluated. Overall 2,517 participants from MESA Lung and 2,339 from SPIROMICS were included. They found the link of higher GRS with lower lung function and increased COPD risk, as well as lower lung density, smaller airway lumens, and fewer small airways; smoking did not modify the effect. In MESA, links between the GRS and FEV1/FVC were attenuated by 100% after adjustment for CT lung structure, especially small airway measures. This attenuation was by 60% in SPIROMICS after adjustment. Findings revealed a link between a GRS related to COPD susceptibility and CT lung structure. Also, the possible importance of lung structure as a mediator of heritability and determinant of personalized COPD risk was suggested.
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