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

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 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

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

Prediction results.

<p>Variance explained (Nagelkerke pseudo-<i>R</i>² from logistic regression) vs. <i>p</i>-value threshold <i>p</i>_T for including SNPs in the score calculation.</p

Descriptive statistics of the sixteen discovery studies and the replication study.

<p>AGES: Age, Gene/Environment Susceptibility–Reykjavik Study; ASPS: Austrian Stroke Prevention Study; ERF: Erasmus Rucphen Family study; GHS: Gutenberg Health Study; H2000: Health 2000; HBCS: Helsinki Birth Cohort Study; HRS: Health and Retirement Study; KORA S4: Cooperative Health Research in the Region of Augsburg; NFBC1966: Northern Finland Birth Cohort 1966; NTR1: Netherlands Twin Register Cohort 1; NTR2: Netherlands Twin Register Cohort 2; RS-I: Rotterdam Study Baseline; RS-II: Rotterdam Study Extension of Baseline; RS-III: Rotterdam Study Young; SardiNIA: SardiNIA Study of Aging; SHIP: Study of Health in Pomerania; THISEAS: The Hellenic study of Interactions between SNPs & Eating in Atherosclerosis Susceptibility; TwinsUK: the UK Adult Twin Registry; YFS: the Cardiovascular Risk in Young Finns Study; STR: Swedish Twin Registry; Cases: number of participants that were at least once self-employed; Controls: number of participants that were not, and ideally never, self-employed; SD: standard deviation.</p>a<p>The number of male participants was insufficient for a male stratified analysis.</p

Manhattan plots of the self-employment discovery meta-analyses.

<p>Manhattan plot of the self-employment discovery meta-analysis for (A) pooled males and females, (B) males only, and (C) females only. SNPs are plotted on the <i>x</i>-axis according to their position on each chromosome against association with self-employment on the <i>y</i>-axis (shown as −log10 <i>p</i>-value). The solid line indicates the threshold for genome-wide significance (<i>p</i><5×10⁻⁸) and the dashed line the threshold for suggestive SNPs (<i>p</i><1×10⁻⁵).</p

Q–Q plots of the self-employment discovery meta-analyses.

<p>Q–Q plot of the self-employment discovery meta-analysis for (A) pooled males and females, (B) males only, and (C) females only. The grey shaded areas in the Q–Q plots represent the 95% confidence bands around the <i>p</i>-values.</p

Variance in the tendency to engage in self-employment explained by all autosomal SNPs in a combined sample of RS-I and STR for pooled males and females, males only, and females only.

<p>The genetic relationships were estimated from 301,115 directly genotyped autosomal SNPs that were available in both studies. All analyses controlled for age, study, and the first 10 principal components of the genetic similarity matrix of the combined sample of RS-I and STR. In the pooled sample we also controlled for sex. The results did not change markedly when 4 or 20 principal components were included; <i>σ_g</i>²/<i>σ_P</i>²: proportion of phenotypic variance explained by the variance of the total additive genetic effects of the 301,115 autosomal SNPs; s.e.: standard error; <i>p</i>-value: <i>p</i>-value from a likelihood ratio (LR) test assuming that the LR is distributed as a 50∶50 mixture of zero and <i>χ</i>₁².</p