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

Genetic Associations and Architecture of Asthma-COPD Overlap

Background Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. Research Question What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma? Study Design and Methods We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P Results We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P Interpretation We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.</p