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

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.

doi:10.1186/s12881-018-0656-z

BMC Medical Genetics

Table 3 Association Results of rs28929474 in SERPINA1 with Lung Function, COPD, and COPD Severity

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

Phenotype	CC (n = 1559)	CT (n = 78)	TT (n = 8)	TT vs. CT vs. CC		CT vs. CC		TT vs. CT		TT vs. CC
Phenotype	CC (n = 1559)	CT (n = 78)	TT (n = 8)	β or OR	P value	β or OR	P value	β or OR	P value	β or OR	P value
Age at enrollment, years	65.4 ± 8.2	64.5 ± 8.1	53.7 ± 3.9	−2.38	0.0029	−0.92	0.33	−10.8	3.6 × 10⁻⁴	−11.7	5.7 × 10⁻⁵
Sex (Female vs. Male), n	696 vs. 863	33 vs. 45	2 vs. 6	0.83	0.35	0.91	0.69	0.46	0.35	0.41	0.28
Pack-years of cigarette smoking	52.3 ± 26.6	48.9 ± 26.4	35.2 ± 13.4	−3.97	0.12	−3.10	0.3	−6.62	0.52	−12.3	0.19
Post-bronchodilator FEV₁/FVC	0.61 ± 0.16	0.54 ± 0.18	0.39 ± 0.09	−0.087	1.2 × 10⁻⁸	− 0.077	2.3 × 10^− 5	−0.090	0.21	−0.23	3.2 × 10^− 5
Pre-bronchodilator FEV₁/FVC	0.59 ± 0.15	0.52 ± 0.17	0.37 ± 0.09	−0.081	9.9 × 10^− 8	−0.069	1.7 × 10^− 4	− 0.086	0.22	−0.22	3.5 × 10^− 5
Post-bronchodilator % predicted FEV₁	72.5 ± 25.6	61.3 ± 26.4	33.5 ± 7.89	−13.6	3.5 × 10^− 8	− 11.4	9.1 × 10^− 5	−22.5	0.037	−38.1	2.2 × 10^− 5
Post-bronchodilator FEV₁, ml	2115 ± 888	1841 ± 860	1210 ± 240	− 439	2.1 × 10⁻⁹	− 329	1.4 × 10^− 4	− 1066	1.5 × 10^− 4	− 1395	1.4 × 10⁻⁷
Pre-bronchodilator % predicted FEV₁	65.6 ± 26.1	54.8 ± 26.9	30.2 ± 7.57	−12.9	8.3 × 10^− 7	−10.9	5.0 × 10^− 4	−17.5	0.12	−34.7	1.6 × 10^− 4
Pre-bronchodilator FEV₁, ml	1916 ± 883	1629 ± 833	1091 ± 240	− 426	1.1 × 10^− 8	− 339	1.2 × 10^− 4	− 924	8.1 × 10^− 4	− 1263	2.9 × 10^− 6
% change in FEV₁ (BDR)	13.6 ± 13.5	17.1 ± 18.1	11.6 ± 9.75	2.08	0.13	3.49	0.030	−3.56	0.65	−2.77	0.57
Post-bronchodilator % predicted FVC	90.7 ± 17.7	86.9 ± 17.2	71.5 ± 21.1	−5.23	0.0024	−3.83	0.060	−18.0	0.019	−17.0	0.0070
Post-bronchodilator FVC, ml	3518 ± 1011	3482 ± 1036	3365 ± 1015	− 236	4.6 × 10^− 4	− 162	0.042	− 661	0.023	− 822	7.1 × 10^− 4
Pre-bronchodilator % predicted FVC	84.4 ± 19.4	78.9 ± 18.6	68.7 ± 21.7	−6.07	0.0018	−5.55	0.017	−12.6	0.13	−14.2	0.038
Pre-bronchodilator FVC, ml	3274 ± 1032	3145 ± 1015	3240 ± 1071	−277	2.0 × 10^− 4	− 249	0.0046	− 434	0.16	− 683	0.011
COPD (GOLD stage 2–4 vs. 0), n	803 vs. 539	53 vs. 20	8 vs. 0	2.31	7.8 × 10⁻⁴	1.91	0.019	NA	NA	NA	NA
COPD severity (GOLD stage 3–4 vs. 1), n	331 vs. 217	32 vs. 5	8 vs. 0	4.08	0.0036	3.79	0.0081	NA	NA	NA	NA

Association analyses of age or sex were performed using linear or logistic regression without adjustment. Association analyses of Pre-/Post-bronchodilator FEV₁ and FVC in ml were performed using linear regression adjusted for sex, age, age², height, height², weight, current smoking status, pack-years of cigarette smoking, and the first two principal components. Association analyses of Pre-/Post-bronchodilator FEV₁, FVC, and FEV₁/FVC, and % change in FEV₁ were performed using linear regression adjusted for age, sex, current smoking status, pack-years of cigarette smoking, and the first two principal components. Association analyses of COPD and COPD severity were performed using logistic regression adjusted for age, sex, current smoking status, pack-years of cigarette smoking, and the first two principal components

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