RegulomeDB functional annotation for SNPs in CTCF and its regulatory regions.

<p>Notes: * genotyped in the BOMA-UTR data set and sorted by their genomic coordinates. SNPs are within or 20 kb upstream and downstream of <i>CTCF</i>. ** <i>AR FOXA1 USF1 CDX2 HNF4A TRIM28 USF2 TCF4 HDAC2 SP1 BHLHE40</i>. *** <i>KROX SP4 SP1:SP3 HIC1 Zif268 Sp4 Sp1 SP1 Egr</i>. § RegulomeDB score: [1f] - likely to affect binding and linked to expression of a gene target; [2b] - likely to affect binding; <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004345#pgen.1004345-Herold1" target="_blank">[4]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004345#pgen.1004345-Wang1" target="_blank">[5]</a>, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004345#pgen.1004345-Ramanan1" target="_blank">[6]</a> - minimum binding evidence.</p

Comparisons of FDRs (BH) and p-values (P) for the BOMA-UTR and the GAIN-MGS data sets for the replicated pathways.

<p>* - Significant pathways identified by more than one pathway analysis method within the BOMA-UTR data set. The test statistics obtained using the alternative algorithms are provided in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004345#pgen.1004345.s004" target="_blank">Table S1B</a>.</p><p>Note: FDR – False Discovery Rate; BH – Benjamini-Hochberg.</p

Flowchart for (1) detection and replication of schizophrenia associated pathways and (2) identification of the most informative genes, and (3) functional annotation of single nucleotide polymorphisms in the genes of interest.

<p>Flowchart for (1) detection and replication of schizophrenia associated pathways and (2) identification of the most informative genes, and (3) functional annotation of single nucleotide polymorphisms in the genes of interest.</p

Description of individual samples.

a<p>Platforms are: I5, Illumina HumanHap 550; I6Q, Illumina Human610 Quad; IWQ, Illumina Human660W-Quad; A6, Affymetrix Genome-Wide Human SNP Array 6.0.</p>b<p>Publication reporting individual sample level genotypes for Schizophrenia is listed.</p><p>Discovery set: single nucleotide polymorphisms (SNPs) before pruning – 491,393; after pruning – 419,267.</p><p>Replication set: SNPs before pruning – 669,059; after pruning – 552,988.</p

Genome-wide association results and detailed peak association regions.

<p>(<b>A</b>) Manhattan plot of the meta-analysis performed on early-onset bipolar patients and controls from France and Germany. Physical position is shown along the <i>x</i> axis and –log10(<i>P</i>-value) is shown along the <i>y</i> axis. (<b>B</b>) Detail of the two most associated regions on chromosomes 5p13 and 12p12. Allele frequency differences are represented by –log10(<i>P</i>-values) for the French (open grey circles), the German (open grey squares) and the meta- (open red diamonds) analyses. Grey crosses represent –log10(<i>P</i>-value) for imputed ungenotyped SNPs. The most associated SNP for each region is shown with orange circle. On chromosome 12p12, the lowest <i>P</i>-value (<i>P</i> = 2.1×10⁻⁷) was observed for an imputed SNP (<i>rs10743315</i>). On chromosome 5p13, the lowest <i>P</i>-value (<i>P</i> = 2.6×10⁻⁷) was observed for a three-SNPs window haplotype (light blue line) located downstream to <i>OXCT1</i> and upstream to <i>PLCXD3</i> (<i>rs624097-rs316762-rs10512793</i>). The genome-wide significant threshold (<i>P</i> = 5×10⁻⁸) is indicated by the blue dash line and the dot black line shows a threshold at <i>P</i> = 5×10⁻⁵. The largest differences in allele frequencies are represented with filled diamonds. Gene position and annotation (<a href="http://genome.ucsc.edu/" target="_blank">http://genome.ucsc.edu/</a>) are symbolised by green arrows. Linkage disequilibrium (r²) estimated according to HapMap CEU population SNPs (release 3) is symbolised in the bottom part of each figure. Darker red indicates higher values.</p

Regions associated at <i>P</i><5×10⁻⁵ with early-onset BD in meta-analysis.

<p>OR, odds ratio; Q, <i>P</i>-value for Cochrane's Q statistic; I², heterogeneity index.</p>a<p>position from the short arm telomere based on Hg18.</p

Origin of the samples used either in the GWAS mining, or genotyped in the replication samples.

<p>The number of cases and controls, number of markers mined/genotyped and the genotyping technology is shown. The covariate code takes into consideration the possible effect of country of origin and platform used in the genotypic analysis.</p>*<p>Same control samples used,</p>**<p>same control samples used. n.a., not applicable as the sample was not used for the merged analyses.</p

Association analyses across ADHD, SCZ and BP phenotypes.

<p>For ADHD+BP, 3462 cases versus 4222 controls were analyzed; for ADHD+SCZ, 3621 cases versus 4793 controls were analyzed; for BP+SCZ, 2092 cases versus 2901 controls were analyzed; for ADHD+BP+SCZ, 4587 cases versus 5308 controls were analyzed. The 11 markers typed in all the samples are presented.</p>*<p>indicates significant P-values (<0.05).</p

Association results for the SCZ cases and control samples.

<p>Analyses are presented for both the allelic regression and the genotypic regression for which the genotypes were recoded under an additive genotypic model; age, sex and country/study were used as covariates. The German sample consists of 484 cases and 1300 controls. The Scandinavian SCOPE (Scandinavian Collaboration on Psychiatric Etiology) sample (Scand.) consists of 641 cases and 1086 controls and was created by merging the Danish and Norwegian samples, which were shown previously to be similar <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035424#pone.0035424-Hansen1" target="_blank">[32]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035424#pone.0035424-LeHellard2" target="_blank">[41]</a>. The 15 markers that were typed or extracted in the 2 samples are presented (1125 cases and 2386 controls); see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035424#pone.0035424.s003" target="_blank">Tables S2</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035424#pone.0035424.s004" target="_blank">S3</a> for results from all markers in each sample. In <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035424#pone-0035424-t002" target="_blank">Tables 2</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035424#pone-0035424-t003" target="_blank">3</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035424#pone-0035424-t004" target="_blank">4</a>, and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035424#pone-0035424-t005" target="_blank">5</a>, the position (hg18, NCBI36) of each marker is given below its rsID, the minor alleles and their frequencies in cases and controls are given, together with the odds ratio, the 95% confidence interval and the genotype success (call rate).</p>*<p>indicates significant P-values (<0.05).</p

Association results for the ADHD cases and control samples.

<p>Analyses are presented for both the allelic regression and the genotypic regression for which the genotypes were recoded under an additive genotypic model; age, sex and country/study were used as covariates. The Norwegian (NO) sample consists of 466 cases and 515 controls; the German (GE) sample consists of 500 cases and 1300 controls. The 12 markers that were typed or extracted in the 2 samples are presented (966 cases and 1815 controls); see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035424#pone.0035424.s007" target="_blank">Tables S6</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035424#pone.0035424.s008" target="_blank">S7</a> for results from all markers in each sample.</p>*<p>indicates significant P-values (<0.05).</p