Details

Autor(en) / Beteiligte

• 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, 3rd, Robert
• Woodruff, Prescott G
• Hawkins, Gregory A
• Bleecker, Eugene R
• Meyers, Deborah A

Titel

Genome-wide association study of lung function and clinical implication in heavy smokers

Ist Teil von

• BMC medical genetics, 2018-08, Vol.19 (1), p.134-10, Article 134

Ort / Verlag

England: BioMed Central Ltd

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The aim of this study is to identify genetic loci associated with post-bronchodilator FEV /FVC and FEV , and develop a multi-gene predictive model for lung function in COPD. Genome-wide association study (GWAS) of post-bronchodilator FEV /FVC and FEV was performed in 1645 non-Hispanic White European descent smokers. A functional rare variant in SERPINA1 (rs28929474: Glu342Lys) was significantly associated with post-bronchodilator FEV /FVC (p = 1.2 × 10 ) and FEV (p = 2.1 × 10 ). In addition, this variant was associated with COPD (OR = 2.3; p = 7.8 × 10 ) 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 FEV /FVC can be explained by SNPs in 10 genes with age, sex, and pack-years of cigarette smoking (P <  2.2 × 10 ). 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.