Adjusted mean values in <b>Δ</b>FEV1 and <b>Δ</b>FVC over 11 years of follow-up comparing different <i>SERPINA1</i> genotypes.

<p>CI: confidence interval. FEV1: forced expiratory volume in 1 second. FVC: forced vital capacity.</p><p>Covariates included sex, linear and squared age, recruiting area, smoking history (packyears at baseline, as well as linear and squared packyears between baseline and follow-up), height, baseline BMI and BMI change between baseline and follow-up.</p>a<p>Passive smokers were defined as never smokers who declared regular exposure to environmental tobacco smoke within one year prior to the baseline or follow-up examination.</p>b<p>Persistent smokers were classified as subjects who declared current smoking at both examinations.</p>c<p>Obese subjects were defined as BMI≥30kg/m² at the baseline or follow-up examination.</p

Adjusted mean values in <b>Δ</b> (FEV1/FVC) and <b>Δ</b>FEF25-75% over 11 years of follow-up comparing different <i>SERPINA1</i> genotypes.

<p>CI: confidence interval. FEF25-75%: forced mid expiratory flow. FEV1: forced expiratory volume in 1 second. FVC: forced vital capacity.</p><p>Covariates included sex, linear and squared age, recruiting area, smoking history (packyears at baseline, as well as linear and squared packyears between baseline and follow-up), height, baseline BMI and BMI change between baseline and follow-up.</p>a<p>Passive smokers were defined as never smokers who declared regular exposure to environmental tobacco smoke within one year prior to the baseline or follow-up examination.</p>b<p>Persistent smokers were classified as subjects who declared current smoking at both examinations.</p>c<p>Obese subjects were defined as BMI≥30kg/m² at the baseline or follow-up examination.</p>d<p>Corresponded to a level of ≥ 1.8 mg/l.</p

Distribution of interaction p-values across genes mapping to pathways with weak interaction signals.

<p>P-values of interaction on the gene-level are given on a minus log₁₀ scale (y-axis), i.e. higher bars represent smaller interaction p-values. (A) Genes of the mitochondrial dysfunction pathway interacting with PM10 and packyears exposure between surveys on FEV₁/FVC decline. (B) Genes of the methane metabolism pathway interacting with PM10 and packyears exposure between surveys on FEF_25–75 decline. (C) Genes of the apoptosis signaling pathway interacting with PM10 and packyears exposure between surveys on FEV₁ decline.</p

Nominally significant gene-environment interactions by outcome and exposure.

<p>Genes are sorted in ascending order of interaction p-value within outcome-exposure strata.</p>a<p>significant after Bonferroni-correction for testing 152 genes (α = .00033).</p>b<p>marginally significant after Bonferroni-correction for testing 152 genes (α = .00033).</p

Distribution of main characteristics by smoking status at follow-up and PM₁₀ exposure during follow-up (N = 650¹).

1<p>restricted to sample with complete data on all three lung function parameters. Regarding FEV₁, sample size with complete covariate data would be n = 669.</p>2<p>means for age and lung function values, medians for pack years exposures.</p

Mapping of candidate oxidative-stress genes to molecular pathways of interest.

<p>Mapping of candidate oxidative-stress genes to molecular pathways of interest.</p

Effect estimates of the strongest interacting SNP from each nominally significant gene on FEV₁/FVC decline (n = 650).

<p>SNP-estimates are based on an additive model. Beta-estimates represent percentages of decline in FEV₁/FVC over 11 years per effect allele and/or for an exposure contrast of one interquartile range (IQR). All estimates are taken from the same interaction model. Positive values mean an attenuation, and negative ones an acceleration of FEV₁/FVC decline. Rows are sorted according to ascending interaction p-values.</p>*<p>significant after Bonferroni correction for testing 12679 SNPs (α = 3.9×10E-6).</p><p>gen: genotyped SNP; imp: imputed SNP; All1: allele 1 (effect allele); All2: allele 2 (baseline allele); FreqAll1: frequency of allele 1.</p

Forest plot of meta-analyzed results for the effect per minor allele of rs3748312 on FEV1 in ever-smokers, adjusted for sex, age, height, population stratification factors and the presence of PI S and Z alleles.

<p>Studies based on population isolates with a high degree of cryptic relatedness are presented separately. Effect estimates of meta-analyses are shown with green diamonds. I² is a measure of the heterogeneity between studies. Random effect meta-analyses are included if I²>0.5. Study weights (blue squares) correspond to fixed effect meta-analyses.</p

Common and low-frequent <i>SERPINA1</i> SNPs and their association with AAT serum level, univariate and conditional on significantly associated SNPs (N = 5569^a), in SAPALDIA.

<p>Abbreviations: AAT, alpha1-antitrypsin; MAF, minor allele frequency; SNP, single nucleotide polymorphism.</p><p>Chromosomal position is based on reference panel, NCBI build 36.3.</p>a<p>Includes subjects for whom all the 16 SNPs have been successfully genotyped.</p>b<p>SNP selection was based on extreme trait sequence data (A), tagging SNPs according to HapMap (B), TAMAL software (C) and publication about functionality (D); see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003585#s4" target="_blank">Materials and Methods</a> for a more detailed description.</p>c<p>Univariate analyses were adjusted for non-genetic factors only (sex, age, recruiting area and current smoking status). Allele effects are shown in absolute numbers and P<0.005 was considered statistically significant.</p>d<p>In a forward selection approach of stepwise regression, the four SNPs in bold contributed statistically significantly to the variability in AAT serum levels and were included in the final statistical model. Allele effects and p-values refer to this final model.</p

Minor allele effects on FEV1 of low-frequent and common SNPs in the <i>SERPINA</i> gene cluster in ever-smokers undergoing lung resection.

<p>Abbreviations: FEV1, forced expiratory volume in one second; MAF, minor allele frequency; SNP, single nucleotide polymorphism.</p><p>Imp-r² is an indicator for imputation quality. The analyses were adjusted for age, sex and height.</p>a<p>Rs4905179 was genotyped in UBC.</p