Hierarchical cluster of the correlation across 43 overlapping metabolites from both platforms.

<p>Upper colour bars represent metabolites with mGWAS results, metabolite type, and metabolite platform. The left colour bar represents the heritability of the metabolite from red (high) to white (low).</p

mGWAS results at 7 loci associated with metabolites in both platforms.

<p>mGWAS results at 7 loci associated with metabolites in both platforms.</p

Participant characteristics (Replication Study).

<p>Values are means ± standard deviation for each quantitative trait.</p

–log₁₀<i>P</i> values of the 5 replicated meQTLs against genomic position, with the top SNP indexed and indicated by a diamond.

<p>Estimated recombination rates are shown in blue, and SNP LD is given by colour as shown in the legends (LD data from 1000 Genomes Nov 2010 CEU genotypes).</p

Genome-wide meQTL analysis. A:

<p><i>Cis</i>-meQTL quantile-quantile plot showing enrichment of association signal. Grey bands correspond to 95% confidence intervals. <b>B:</b> Significant meQTL are located close to CpG sites.</p

Flowchart showing the analysis pipeline.

<p><b>Top:</b> Association of DMH Methylation Score with phenotypes. <b>Bottom:</b> Primary <i>cis</i>-meQTL association study, followed by replication study. <b>Left:</b> Association of DMH probe sets with significant meQTLs with mRNA expression. <b>Right:</b> Text mining of meQTLs significant in the primary study.</p

Boxplots showing methylation level plotted against genotype for the 5 replicated meQTLs in both the primary study (left panels) and replication study (right panels).

<p>All SNPs passed quality control filtering and association with methylation levels in both data sets.</p

Replicated meQTL hits.

<p>a) ID of probe set on DMH array,</p><p>b) chromosome.</p><p>c) genomic coordinates of probe set in build37.</p><p>d) genomic coordinates of SNP in build37.</p><p>e) coefficient of SNP effect.</p><p>f) standard error for the SNP effect.</p><p>g) p-value for the SNP effect.</p><p>h) ID of probe on Illumina 27k array,</p><p>i) genomic coordinates of CpG probed in build37.</p><p>j) one-sided p-value for the SNP effect in the direction of the original association.</p

The <i>SPTA1</i> gene is transcriptionally regulated by <i>TAF3</i>.

<p>(A) Knockdown of <i>TAF3</i> by shRNA and its effect on <i>SPTA1</i> expression in human K562 cells, and in differentiating mouse MEL cells. 4 days after induction. Expression was monitored by qRT-PCR. NS: control scrambled shRNA; <i>TAF3</i>kd1 and <i>TAF3</i> kd2 and anti <i>Taf3</i> shRNAs described in Methods. (B) Chromatin immunoprecipitation analysis of the recruitment of <i>TAF3</i> and <i>TBP</i> to the indicated promoters in K562 cells shows that <i>TAF3</i> is associated with <i>SPTA1</i>. <i>TAF3</i>: ChIP with anti Taf3 Ab; IgG: control chromatin immunoprecipitation with IgG addition. Asterisks indicate a statistical significant difference (*  = <i>P</i><0.05; **  = <i>P</i><0.01) between control and TAF3 knockdown data for MEL and K562 cells, and between specific immunoprecipitations and IgG control immunoprecipitations.</p

rs1887582 association in general population cohorts.

<p>rs1887582 association in general population cohorts.</p