Modules for which eigengenes were significantly correlated (FDR p<0.01) with MetS in ABD (N = 9) and GLU (N = 6).

<p>FDR corrected pvalues for the associations with MetS and six quantitative metabolic traits are shown.</p><p>*DE = differentially expressed between adipose depots;</p><p>**Diast bp = diastolic blood pressure;</p><p>***Syst bp = systolic blood pressure.</p

Sources of gene expression variation in different tissues.

<p>A) 626 probesets associated with MetS in MolOBB ABD B) 205 probesets associated with MetS in MolOBB GLU. Variances are decomposed in MolTWIN ABD and WB.</p

Biological Processes GO terms were significantly enriched (FDR P<0.01) in 15 modules associated with MetS in ABD and GLU.

<p>*P value = Fisher Exact Test;</p><p>**FE = Fold Enrichment.</p

Characteristics of the participants included in ABD gene expression analyses (with both nonmissing expression and phenotype data).

<p>Values are means ± standard deviation for each quantitative variable.</p><p>*Individuals (N = 7) with treatment for lipid abnormalities or hypertension were assigned as having reduced HDL or raised blood pressure. T2D is defined as fasting blood glucose >7.0 mmol/l or antiglycemic treatment).</p

Gene expression changes related to MetS in ABD and GLU.

<p>A,B. Heatmap of scaled expression values of 893 and 335 differentially expressed genes between MetS cases and controls in ABD (A) and GLU (B) samples. The dendogram depicts hierarchical clustering of the differentially expressed genes. The bottom bars show black boxes for MetS, the presence of the MetS components (reduced HDL, raised TG, raised fasting glucose, raised blood pressure) and gender (females). C. The top 10 genes differentially expressed in ABD and the top 10 genes differentially expressed in GLU. The horizontal bars displays −log₁₀ Pvalues for differential expression between MetS cases and controls in ABD and GLU and between depots.</p

Summary of <i>cis</i> eQTL results for selected expression probes significantly associated with MetS and showing differential ABD-GLU expression in MolOBB network and single-gene association analyses (FDR P<0.01).

<p>Independent association between the <i>cis</i> eQTL SNPs and metabolic traits was assessed in two GWA datasets.</p><p>DE = differential expression;</p><p>*genomic control adjusted pvalues from GIANT consortium;</p><p>**genomic control adjusted pvalues from <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002505#pgen.1002505-Teslovich1" target="_blank">[4]</a>.</p

MetS-associated modules found in the different fat depots.

<p>Visualization of the ABD brown (A), GLU darkgreen (B), consensus yellow in ABD (C) and consensus yellow in GLU (D) modules, respectively. For each module the top 150 pairwise correlations (intramodular connectivities) are shown. Genes with the top 10 highest ranked module membership are displayed in larger circles.</p

Seven SNPs show sex difference.

a<p>Trait and sex for which the SNP was selected;</p>b<p>Gene labels state the nearest gene or the gene as published previously; details on all genes near the association signal can be found in the <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003500#pgen.1003500.s002" target="_blank">Figure S2</a>;</p>c<p>One-sided P-Values.</p>d<p>larger sample size due to one additional study that did not have hip circumference, and therefore could not contribute to WHRadjBMI.</p>e<p>smaller sample size as this SNP was not on Metabochip.</p><p>Shown are the seven SNPs with significant (at 5% false discovery rate) sex difference in the follow-up data. These seven SNPs exhibit genome-wide significant association in women (joint discovery and follow-up <i>P_women</i><5×10−8) and only two of these show nominally significant association in men (joint <i>P_men</i><0.05). The three loci MAP3K1, HSD17B4, and PPARG are shown here for the first time for their anthropometric trait association as well as for sex-difference.</p

Seven identified SNPs compared to previously published loci.

a<p>The Effect allele refers to a positive effect direction in the discovery stage for the trait and gender, the SNP was selected for;</p>b<p>Gene near this SNP which was published previously from sex-combined analyses.</p><p>The seven SNPs with sex difference are considered to depict a known locus, if the index SNP is close to a published top SNP (<1 cM). These include four of the previously reported sexually dimorphic WHR loci (Heid et al., Nat Genet 2010).</p

Genome-wide scan for sex-specific genome-wide association highlights numerous loci.

<p>(a) Manhattan plot showing the men-specific (upward, up to 60,586 men) and women-specific (downward, up to 73,137 women) association P-values from the discovery with the 619 selected loci colored by the phenotype for which the locus was selected; (b) QQ-plot showing the sex-specific association P-values as observed against those expected under the null overall phenotypes (black) and for each phenotypes separately (colored).</p