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

Summary of Metabochip SNPs by SNP category.

<p> <i>Numbers in parenthesis represents the proportion of the SNPs in the previous column. A SNP may fall into multiple categories.</i></p

Coverage of 257 Metabochip fine-mapping regions.

<p>Fraction of 1000 Genomes Project SNPs in strong linkage disequilibrium (r²≥.8) with HapMap 3 (green squares) or Metabochip (blue dots) SNPs as a function of minor allele frequencies: (A) 1000 Genomes Pilot 1 SNPs, (B) 1000 Genomes Phase 1 SNPs (May 2011 release).</p

Summary of Metabochip SNPs by trait: Fine-mapping and replication.

<p> <i>SNP counts are numbers of SNPs successfully manufactured on the Metabochip array.</i></p>*<p> <i>Waist-to-hip ratio and waist circumference were adjusted for body mass index.</i></p

Regional association plots for LDL cholesterol association in the SardiNIA study.

<p>Association plots for a study of 2,432 Sardinian individuals for five Metabochip fine-mapping regions using 1000 Genomes data as reference set and Affymetrix genotypes (left panels : A,C,E,G,H) or Metabochip genotypes (right panels : B,D,F,H,J) as target sets. The figures plot −log₁₀ of the association p-value within the region and recombination rate (blue lines) as a function of position on the chromosome. Blue, green, and red dots and triangles indicate genotyped and imputed SNPs with minor allele frequencies less than 0.02, greater than or equal 0.02 and less than 0.05, and greater than or equal 0.05, respectively. Gene positions and structures are displayed in the lower panel.</p

Example of signal fine mapping (SFM) and locus fine mapping (LFM) regions.

<p>A SFM region seeks to map the initial association signal. SFM regions were designed using linkage disequilibrium (LD) r² estimates from the 1000 Genomes Project and HapMap CEU data. Initial boundaries were determined by identifying all SNPs satisfying r²≥.5 with the index SNP, and then expanded to the nearest flanking recombination hotspot, but stopped if there was no hotspot nearby. LFM regions (blue) were similarly designed but expanded to capture functional units of interest such as nearby coding genes. The figure plots LD r² for SNPs (red dots) within the region and recombination rate (blue lines) as a function of position on the chromosome. Gene positions and structures are displayed in the lower panel. MI = myocardial Infarction; CAD = cardiovascular disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein; T2D = type 2 diabetes.</p