Genome-wide association study of lung function and clinical implication in heavy smokers
dc.contributor.author | Li, Xingnan | |
dc.contributor.author | Ortega, Victor E | |
dc.contributor.author | Ampleford, Elizabeth J | |
dc.contributor.author | Graham Barr, R. | |
dc.contributor.author | Christenson, Stephanie A | |
dc.contributor.author | Cooper, Christopher B | |
dc.contributor.author | Couper, David | |
dc.contributor.author | Dransfield, Mark T | |
dc.contributor.author | Han, Mei L K | |
dc.contributor.author | Hansel, Nadia N | |
dc.contributor.author | Hoffman, Eric A | |
dc.contributor.author | Kanner, Richard E | |
dc.contributor.author | Kleerup, Eric C | |
dc.contributor.author | Martinez, Fernando J | |
dc.contributor.author | Paine, Robert | |
dc.contributor.author | Woodruff, Prescott G | |
dc.contributor.author | Hawkins, Gregory A | |
dc.contributor.author | Bleecker, Eugene R | |
dc.contributor.author | Meyers, Deborah A | |
dc.date.accessioned | 2018-08-05T03:50:38Z | |
dc.date.available | 2018-08-05T03:50:38Z | |
dc.date.issued | 2018-08-01 | |
dc.identifier.citation | BMC Medical Genetics. 2018 Aug 01;19(1):134 | |
dc.identifier.uri | https://doi.org/10.1186/s12881-018-0656-z | |
dc.identifier.uri | https://hdl.handle.net/2027.42/145186 | |
dc.description.abstract | 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. | |
dc.title | Genome-wide association study of lung function and clinical implication in heavy smokers | |
dc.type | Article | en_US |
dc.description.bitstreamurl | https://deepblue.lib.umich.edu/bitstream/2027.42/145186/1/12881_2018_Article_656.pdf | |
dc.language.rfc3066 | en | |
dc.rights.holder | The Author(s). | |
dc.date.updated | 2018-08-05T03:50:39Z | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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