Journal article
Genome-wide association study of lung function and clinical implication in heavy smokers
BMC medical genetics, Vol.19(1), pp.134-134
08/01/2018
DOI: 10.1186/s12881-018-0656-z
PMCID: PMC6090900
PMID: 30068317
Abstract
Background
The aim of this study is to identify genetic loci associated with post-bronchodilator FEV1/FVC and FEV1, and develop a multi-gene predictive model for lung function in COPD.
Methods
Genome-wide association study (GWAS) of post-bronchodilator FEV1/FVC and FEV1 was performed in 1645 non-Hispanic White European descent smokers.
Results
A functional rare variant in SERPINA1 (rs28929474: Glu342Lys) was significantly associated with post-bronchodilator FEV1/FVC (p = 1.2 × 10− 8) and FEV1 (p = 2.1 × 10− 9). In addition, this variant was associated with COPD (OR = 2.3; p = 7.8 × 10− 4) and severity (OR = 4.1; p = 0.0036). Heterozygous subjects (CT genotype) had significantly lower lung function and higher percentage of COPD and more severe COPD than subjects with the CC genotype. 8.6% of the variance of post-bronchodilator FEV1/FVC can be explained by SNPs in 10 genes with age, sex, and pack-years of cigarette smoking (P < 2.2 × 10− 16).
Conclusions
This study is the first to show genome-wide significant association of rs28929474 in SERPINA1 with lung function. Of clinical importance, heterozygotes of rs28929474 (4.7% of subjects) have significantly reduced pulmonary function, demonstrating a major impact in smokers. The multi-gene model is significantly associated with CT-based emphysema and clinical outcome measures of severity. Combining genetic information with demographic and environmental factors will further increase the predictive power for assessing reduced lung function and COPD severity.
Details
- Title: Subtitle
- Genome-wide association study of lung function and clinical implication in heavy smokers
- Creators
- Xingnan Li - Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, BioScience Research Lab, Tucson, USAVictor E. Ortega - Wake Forest UniversityElizabeth J. Ampleford - Wake Forest UniversityR. Graham Barr - New York, NY USAStephanie A. Christenson - University of California, San FranciscoChristopher B. Cooper - University of California, Los AngelesDavid Couper - University of North Carolina at Chapel HillMark T. Dransfield - University of Alabama at BirminghamMei Lan K. Han - Ann Arbor, MI USANadia N. Hansel - Johns Hopkins MedicineEric A. Hoffman - University of IowaRichard E. Kanner - University of UtahEric C. Kleerup - University of California, Los AngelesFernando J. Martinez - Cornell UniversityRobert Paine - University of UtahPrescott G. Woodruff - University of California, San FranciscoGregory A. Hawkins - Wake Forest UniversityEugene R. Bleecker - University of ArizonaDeborah A. Meyers - University of ArizonaSubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Research Group
- Resource Type
- Journal article
- Publication Details
- BMC medical genetics, Vol.19(1), pp.134-134
- DOI
- 10.1186/s12881-018-0656-z
- PMID
- 30068317
- PMCID
- PMC6090900
- NLM abbreviation
- BMC Med Genet
- ISSN
- 1471-2350
- eISSN
- 1471-2350
- Publisher
- BioMed Central
- Grant note
- HHSN268200900013C; HHSN268200900014C; HHSN268200900015C; HHSN268200900016C; HHSN268200900017C; HHSN268200900018C; HHSN268200900019C; HHSN268200900020C / ;
- Language
- English
- Date published
- 08/01/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984318799502771
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