Genome-wide association study of lung function and clinical implication in heavy smokers
| Autor: | Li, Xingnan, Ortega, Victor E, Ampleford, Elizabeth J, Graham Barr, R, Christenson, Stephanie A, Cooper, Christopher B, Couper, David, Dransfield, Mark T, Han, Mei Lan K, Hansel, Nadia N, Hoffman, Eric A, Kanner, Richard E, Kleerup, Eric C, Martinez, Fernando J, Paine, Robert, Woodruff, Prescott G, Hawkins, Gregory A, Bleecker, Eugene R, Meyers, Deborah A, SPIROMICS Research Group |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Chronic Obstructive Genotype rs28929474 European Continental Ancestry Group Clinical Sciences Pulmonary Disease Genetics Humans COPD GWAS Longitudinal Studies Prospective Studies Polymorphism Lung Aged Genetics & Heredity Smokers Smoking SPIROMICS Research Group Single Nucleotide respiratory system Middle Aged Lung function respiratory tract diseases Respiratory Function Tests Genetic Loci alpha 1-Antitrypsin Female SERPINA1 Genome-Wide Association Study SPIROMICS |
| Zdroj: | BMC medical genetics, vol 19, iss 1 |
| Popis: | BackgroundThe 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.MethodsGenome-wide association study (GWAS) of post-bronchodilator FEV1/FVC and FEV1 was performed in 1645 non-Hispanic White European descent smokers.ResultsA 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 |
| Databáze: | OpenAIRE |
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