Zoom views of the association results in the loci associated with IL-6 and ESR.

<p>Each panel shows the association curve around the strongest SNP, which is highlighted with a purple dot. The SNPs are coloured according to their linkage disequilibrium (r²) with the top variant in the 1000 Genomes European data set, with symbols that reflect genomic annotation as indicated in the legend. Arrows highlight independent signals, if any, described in the manuscript; while light blue lines indicate the recombination rate, according to the right-hand Y axis. Genomic positions are as in build 37. Gene transcripts are annotated in the lower box. Plots were drawn using the standalone LocusZoom version <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002480#pgen.1002480-Pruim1" target="_blank">[65]</a>.</p

Top genome-wide association results for IL-6, ESR, MCP-1, and hsCRP.

<p>The table summarizes top genome-wide association signals for IL-6, ESR, MCP-1 and hsCRP phenotypes in the HapMap based GWAS (Step 1), as well as results in the replication independent cohort (Step 2) and in the combined data-sets. For each marker, frequency and effect estimates are given with respect to the minor allele. Imputation quality scores (RSQ) are reported for imputed SNPs. Novel signals are indicated in bold.</p>a<p>The effect size is measured in standard deviation units, being estimated as the β coefficient of the regression model when using the normalized trait (e.g. an effect size of 1.0 implies each additional copy of the allele being evaluated increases trait values by 1.0 standard deviations).</p>b<p>Independent signals.</p

Manhattan plot and QQ plot of association findings.

<p>The figure summarizes the association results obtained on the ImmunoChip and MetaboChip markers (Step 3). The blue dotted line marks the Bonferroni threshold significance levels (1.7×10⁻⁷), and SNPs in loci exceeding this threshold are highlighted in green. The bottom panel represents the QQ plot, where the red line corresponds to all test statistics, and the blue line to results after excluding statistics at top markers (highlighted in green in the Manhattan Plot). The gray area corresponds to the 90% confidence region from a null distribution of P values (generated from 100 simulations).</p

Zoom views of the association results in the loci associated with MCP-1 and hsCRP.

<p>Each panel shows the association curve around the strongest SNP, which is highlighted with a purple dot. The SNPs are coloured according to their linkage disequilibrium (r²) with the top variant in the 1000 Genomes European data set, with symbols that reflect genomic annotation as indicated in the legend. Arrows highlight independent signals, if any, described in the manuscript; while light blue lines indicate the recombination rate, according to the right-hand Y axis. Genomic positions are as in build 37. Gene transcripts are annotated in the lower box. Plots were drawn using the standalone LocusZoom version <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002480#pgen.1002480-Pruim1" target="_blank">[65]</a>.</p

Top association signals for IL-6, ESR, MCP-1, and hsCRP in the ImmunoChip and MetaboChip data-sets.

<p>The table summarizes top association signals for IL-6, ESR, MCP-1 and hsCRP phenotypes in the ImmunoChip and MetaboChip data-sets (Step 3). For each marker, frequency and effect estimates are given with respect to the minor allele. We also reported the r² with the SNP detected in the GWAS scan (Step 1). Novel signals are indicated in bold.</p>a<p>The effect size is measured in standard deviation units, being estimated as the β coefficient of the regression model when using the normalized trait (e.g. an effect size of 1.0 implies each additional copy of the allele being evaluated increases trait values by 1.0 standard deviations).</p>b<p>I =  ImmunoChip, M =  MetaboChip.</p>c<p>The table reports the pvalue on the primary analysis. On the conditional analysis, the pvalue for the independent SNPs were: rs12378220, 9.43×10⁻⁰⁸; rs3093077, 9.02×10⁻¹¹; rs2259816, 7.58×10⁻¹⁰.</p>d<p>Independent signals.</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

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

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

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