Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria-0

<p><b>Copyright information:</b></p><p>Taken from "Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria"</p><p>Environmental Health Perspectives 2005;113(6):767-770.</p><p>Published online 10 Feb 2005</p><p>PMCID:PMC1257604.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria-1

<p><b>Copyright information:</b></p><p>Taken from "Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria"</p><p>Environmental Health Perspectives 2005;113(6):767-770.</p><p>Published online 10 Feb 2005</p><p>PMCID:PMC1257604.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria-2

<p><b>Copyright information:</b></p><p>Taken from "Hypersensitivity Pneumonitis Associated with Environmental Mycobacteria"</p><p>Environmental Health Perspectives 2005;113(6):767-770.</p><p>Published online 10 Feb 2005</p><p>PMCID:PMC1257604.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.</p

Additional file 1: of Spirometric variability in smokers: transitions in COPD diagnosis in a five-year longitudinal study

Online Data Supplement. (DOCX 831 kb

Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects

Association of the most statistically significant SNPs with the rate of change in FEV₁ (mL/year) in the meta-analysis of the five cohort studies with ≥3 FEV₁ measurements per participant (n = 10,476).

<p><i>Definition of abbreviations</i>: Chr  =  chromosome; SE  =  standard error; SNP  =  single-nucleotide polymorphism.</p><p>^*Data reported are the meta-analysis results of the SNP-by-time interaction term from the GWAS mixed effects model. A positive β-coefficient indicates an attenuation of FEV₁ decline and a negative β-coefficient an acceleration of FEV₁ decline.</p

Association of the chromosome 15 locus with the rate of change in FEV₁ in the meta-analysis of 14 cohort studies.

<p><b>A</b>) Regional association plot, where the X-axis is Megabase (Mb) position and Y-axes are the negative log of the <i>P</i> value on the left and recombination rate on the right. The sentinel SNP is colored in purple and linkage disequilibrium to the sentinel SNP is depicted by degree of color according to the legend. <b>B</b>) Forest plot for rs4077833, where the size of the square for each study represents its contributing weight to the meta-analysis.</p

Association of the chromosome 11 locus with the rate of change in FEV₁ in the meta-analysis of the five cohort studies with ≥3 FEV₁ measurements per participant.

<p><b>A</b>) Regional association plot, where the X-axis is Megabase (Mb) position, and the Y-axes are the negative log of the <i>P</i> value on the left and recombination rate on the right. The sentinel SNP is colored in purple and linkage disequilibrium to the sentinel SNP is depicted by degree of color according to the legend. <b>B</b>) Forest plot for rs507211, where the size of the square for each study represents its contributing weight to the meta-analysis.</p

Baseline characteristics of cohort studies included in the meta-analysis^*.

<p><i>Definition of abbreviations</i>: ARIC  =  Atherosclerosis Risk in Communities; B58C  =  British 1958 Birth Cohort; BHS  =  Busselton Health Study; CARDIA  =  Coronary Artery Risk Development in Young Adults; CHS  =  Cardiovascular Health Study  =  FHS, Framingham Heart Study; Health ABC  =  Health, Aging, and Body Composition; KORA  =  Cooperative Health Research in the Region of Augsburg; LBC1921  =  Lothian Birth Cohort 1921; LBC1936  =  Lothian Birth Cohort 1936; PIVUS  =  Prospective Investigation of the Vasculature in Uppsala Seniors; RS  =  Rotterdam Study; SAPALDIA  =  Swiss Study on Air Pollution and Lung Diseases in Adults; SD  =  standard deviation; SHIP  =  Study of Health in Pomerania.</p><p>^*Data are presented as mean (SD) unless otherwise indicated; total no. participants  =  27,249, total no. FEV₁ measurements  =  62,130.</p>†<p>Pack-years are calculated among current and former smokers at study baseline.</p

Association of the most statistically significant SNPs with the rate of change in FEV₁ (mL/year) in the meta-analysis of 14 cohort studies (n = 27,249)^*.

<p><i>Definition of abbreviations</i>: Chr  =  chromosome; SE  =  standard error; SNP  =  single-nucleotide polymorphism.</p><p>^*Data reported are the meta-analysis results of the SNP-by-time interaction term from the GWAS mixed effects model. A positive β-coefficient indicates an attenuation of FEV₁ decline and a negative β-coefficient an acceleration of FEV₁ decline.</p