Journal article
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, Vol.200(6), pp.721-731
09/15/2019
DOI: 10.1164/rccm.201812-2355OC
PMCID: PMC6775892
PMID: 30925230
Abstract
Chronic obstructive pulmonary disease (COPD) has been associated with numerous genetic variants, yet the extent to which its genetic risk is mediated by variation in lung structure remains unknown.
To characterize associations between a genetic risk score (GRS) associated with COPD susceptibility and lung structure on computed tomography (CT).
We analyzed data from MESA Lung (Multi-Ethnic Study of Atherosclerosis Lung Study), a U.S. general population-based cohort, and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). A weighted GRS was calculated from 83 SNPs that were previously associated with lung function. Lung density, spatially matched airway dimensions, and airway counts were assessed on full-lung CT. Generalized linear models were adjusted for age, age squared, sex, height, principal components of genetic ancestry, smoking status, pack-years, CT model, milliamperes, and total lung volume.
MESA Lung and SPIROMICS contributed 2,517 and 2,339 participants, respectively. Higher GRS was associated with lower lung function and increased COPD risk, as well as lower lung density, smaller airway lumens, and fewer small airways, without effect modification by smoking. Adjustment for CT lung structure, particularly small airway measures, attenuated associations between the GRS and FEV
/FVC by 100% and 60% in MESA and SPIROMICS, respectively. Lung structure (
< 0.0001), but not the GRS (
> 0.10), improved discrimination of moderate-to-severe COPD cases relative to clinical factors alone.
A GRS associated with COPD susceptibility was associated with CT lung structure. Lung structure may be an important mediator of heritability and determinant of personalized COPD risk.
Details
- Title: Subtitle
- A Genetic Risk Score Associated with Chronic Obstructive Pulmonary Disease Susceptibility and Lung Structure on Computed Tomography
- Creators
- Elizabeth C Oelsner - Columbia UniversityVictor E Ortega - Wake Forest UniversityBenjamin M Smith - Columbia UniversityJennifer N Nguyen - University of VirginiaAni W Manichaikul - University of VirginiaEric A Hoffman - University of IowaXiuqing Guo - The Lundquist InstituteKent D Taylor - The Lundquist InstitutePrescott G Woodruff - University of California, San FranciscoDavid J Couper - University of North Carolina at Chapel HillNadia N Hansel - Johns Hopkins UniversityFernando J Martinez - Cornell UniversityRobert Paine III - University of UtahMeilan K Han - Michigan MedicineChristopher Cooper - University of California, Los AngelesMark T Dransfield - University of Alabama at BirminghamGerard Criner - Temple UniversityJerry A Krishnan - University of Illinois ChicagoRussell Bowler - National Jewish HealthEugene R Bleecker - University of ArizonaStephen Peters - Wake Forest UniversityStephen S Rich - University of VirginiaDeborah A Meyers - University of ArizonaJerome I Rotter - The Lundquist InstituteR Graham Barr - Columbia University
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory and critical care medicine, Vol.200(6), pp.721-731
- DOI
- 10.1164/rccm.201812-2355OC
- PMID
- 30925230
- PMCID
- PMC6775892
- NLM abbreviation
- Am J Respir Crit Care Med
- ISSN
- 1073-449X
- eISSN
- 1535-4970
- Grant note
- U24 HL141762 / NHLBI NIH HHS U01 HL137880 / NHLBI NIH HHS S10 OD018526 / NIH HHS R01 HL077612 / NHLBI NIH HHS R01 HL130506 / NHLBI NIH HHS K23 HL130627 / NHLBI NIH HHS R01 HL131565 / NHLBI NIH HHS R01 HL093081 / NHLBI NIH HHS P30 ES006694 / NIEHS NIH HHS R01 HL112986 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS K24 HL137013 / NHLBI NIH HHS
- Language
- English
- Date published
- 09/15/2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984318702702771
Metrics
18 Record Views