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

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

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

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

Regional plot for the <i>SERPINA</i> gene cluster (93.8–94.2 Mb on chromosome 14q32.13, reference panel: NCBI build 36.3).

<p>Presented are -log(10) p-values and LD (r²) with top-ranking SNP rs2736887 (purple diamond) for all SNPs in this region. The blue line shows recombination rate.</p

LD plot among common and low-frequent SNPs in the <i>SERPINA1</i> gene within the SAPALDIA study.

<p>Shading represent r² values, whereas numbers represent D′ values (no number equals D′ = 1). Red framed SNPs are independently associated with AAT serum levels after forward selection stepwise regression modeling. Rs17580 is the PI S variant and rs28929474 is the PI Z variant.</p

Forest plot of meta-analyzed results for the effect per minor allele of rs4905179 on FEV1 in ever-smokers, adjusted for sex, age, height and population stratification factors.

<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

The ten most strongly associated SNPs in the unconditional GWAS on AAT serum level in SAPALDIA (N = 1392).

<p>Abbreviations: AAT, alpha1-antitrypsin; GWAS, genome-wide association study; MAF, minor allele frequency; SNP, single nucleotide polymorphism.</p><p>Imp-r² is an indicator for imputation quality. SNPs with MAF<0.05 or imp-r²<0.5 were excluded.</p><p>Chromosomal position is based on reference panel, NCBI build 36.3. Allele effects are shown in absolute numbers.</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