Hookworms <i>(Ancylostoma caninum)</i> Attached to the Intestinal Mucosa

<p>Barely visible larvae penetrate the skin (often through bare feet), are carried to the lungs, migrate through the respiratory tract to the mouth, are swallowed, and eventually reach the small intestine. This journey takes about a week. (Photo: Centers for Disease Control)</p

Meta-analysis of genome-wide linkage studies of asthma and related traits-1

Test response. A p(SR) of p < 0.000417 = significant linkage, p < 0.0083 = suggestive linkage. p(SR) & p(OR) data were transformed using f(x) = 0.05/x and plotted on a logscale to improve clarity.<p><b>Copyright information:</b></p><p>Taken from "Meta-analysis of genome-wide linkage studies of asthma and related traits"</p><p>http://respiratory-research.com/content/9/1/38</p><p>Respiratory Research 2008;9(1):38-38.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2391165.</p><p></p

Meta-analysis of genome-wide linkage studies of asthma and related traits-0

Test response. A p(SR) of p < 0.000417 = significant linkage, p < 0.0083 = suggestive linkage. p(SR) & p(OR) data were transformed using f(x) = 0.05/x and plotted on a logscale to improve clarity.<p><b>Copyright information:</b></p><p>Taken from "Meta-analysis of genome-wide linkage studies of asthma and related traits"</p><p>http://respiratory-research.com/content/9/1/38</p><p>Respiratory Research 2008;9(1):38-38.</p><p>Published online 28 Apr 2008</p><p>PMCID:PMC2391165.</p><p></p

Prevalence of AR in ECRHS I Screening by Centre

<p>Centres are sorted by increasing geographical latitudes from left to right.</p

World Map and European Map of Study Centres

<p>World Map and European Map of Study Centres</p

Replication results for top signals from APCAT (Stage1 <i>N</i> = 18,604) in additional studies (Stage 2 <i>N</i> = 15,576) and in GABRIEL.

a<p>Positions/alleles are relative to the forward strand of NCBI build36. ^b,cResults from GABRIEL are from a re-analysis using fixed-effects meta-analysis, excluding the B58C and ECRHS2 cohorts which are included in Stage2 or with occupational asthma (see Methods), and are for the APCAT SNP or the best available proxy. All p values are two-tailed.</p

Characteristics of Stage1 and Stage2 studies.

a<p>See <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044008#pone.0044008.s005" target="_blank">Table S1</a></b> for more information on genotyping, imputation and software used. ^b The characteristics of the studies in the AAGC are presented in Ferreira et al., 2011 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044008#pone.0044008-Ferreira1" target="_blank">[8]</a>. ^c EPIC = European Prospective Investigation into Cancer and Nutrition.</p

Results in APCAT for SNPs at loci with strong previously published evidence of association with asthma.

a<p>Gene shown is nearest gene to associated SNP. SNPs from the same locus are grouped together. ^bReferences: 1 = Moffatt et al. (2010) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044008#pone.0044008-Moffatt2" target="_blank">[17]</a>; 2 = Moffatt et al. (2007) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044008#pone.0044008-Moffatt1" target="_blank">[7]</a>; 3 = Gudbjartsson et al. (2009) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044008#pone.0044008-Gudbjartsson1" target="_blank">[16]</a>; 4 = Sleiman et al (2010) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044008#pone.0044008-Sleiman1" target="_blank">[13]</a>; 5 = Himes et al (2009) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044008#pone.0044008-Himes1" target="_blank">[12]</a>; 6 = Li et al. (2010) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044008#pone.0044008-LangoAllen1" target="_blank">[22]</a>.^cAlleles are indexed to the forward strand of NCBI build36. ^dAPCAT <i>P</i> values are one-tailed with respect to the direction of the original association.^e<i>P</i> values are from fixed-effect inverse-variance model of meta analysis. ^fResults shown are from Moffatt et al (2010), which is the larger and more recent study. ^g SNP rs9273349 is present in NFBC1966 data set only. ^hResults exclude the Framingham Heart Study, which contributed to the original report in Himes et al (2009) ^IShown here are the random effects <i>P</i> value in Gabriel data, the <i>P</i> value for fixed effects model had a genome wide significance <i>P</i> value of 1.4E-08 with no evidence of heterogeneity.</p

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

Regional association plots of novel loci implicated for pulmonary function.

<p>Three novel loci contained SNPs associated with FEV₁/FVC or FEV₁ at the standard genome-wide significance threshold (<i>P</i>&lt;5×10⁻⁸) in joint meta-analyses of SNP and SNP-by-smoking interaction. SNPs are shown within 500 kb of the most significant SNPs on chromosomes (A) 2q36.3 associated with FEV₁/FVC, (B) 6p21.32 associated with FEV₁/FVC, and (C) 17q24.3 associated with FEV₁. Pairwise r² values were based on the HapMap CEU population, and progressively darker shades of red indicate higher r² values. Estimated recombination rates from HapMap are shown as background lines.</p