Percent agreement by educational level for selected items.

<p>Percent agreement by educational level for selected items.</p

Percent agreement by professional role in the healthcare system for selected items.

<p>Percent agreement by professional role in the healthcare system for selected items.</p

Descriptive measures of the sample.

<p>Descriptive measures of the sample.</p

The wish to know in different diagnostic scenarios.

<p>The wish to know in different diagnostic scenarios.</p

CNVs in regions previously associated with SCZ.

<p>SCZ, schizophrenia; del, microdeletion; dup, microduplication; P, P-value; OR, odds ratio. Position according to NCBI built 36; all P-values and ORs were calculated using Fisher's exact test.</p><p>Two of the patients with a deletion in 1q21.1 and one patient with a deletion in 15q11.2 were already reported by Stefansson et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064035#pone.0064035-Stefansson1" target="_blank">[3]</a>, three patients with a deletion in Neurexin were included in Rujescu et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064035#pone.0064035-Rujescu1" target="_blank">[5]</a> and two patients with a deletion and one patient with a duplication in 16p13.11 were part of the study performed by Ingason et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064035#pone.0064035-Ingason1" target="_blank">[10]</a>.</p

Phenotypic information of patients with a CNV in regions previously associated with SCZ.

<p>Chr, chromosome; DEL, deletion; DUP, duplication; Diagnosis, DSM-IV diagnosis; f, female; m, male; AAO, age-at-onset; Family history SCZ, any fist degree relative with schizophrenia; ., missing data; Position according to NCBI built 36.</p

GSEA of differentially expressed cortical genes in psychiatric disorders and non-psychiatric phenotypes.

<p>GSEA was used to analyse the differentially expressed cortical genes, as gene sets, for enrichment of association signal in three different BP GWASs (a German sample, the Norwegian TOP sample and the British WTCCC BP sample <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-Cichon1" target="_blank">[20]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-Djurovic1" target="_blank">[41]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-WTCCC1" target="_blank">[42]</a>), three SCZ GWASs (the Norwegian TOP sample, the German part of a combined German-Dutch SCZ GWAS and a Danish sample <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-Rietschel1" target="_blank">[19]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-Athanasiu1" target="_blank">[43]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-Ingason1" target="_blank">[44]</a>) and six non-psychiatric phenotypes (from WTCCC; CD: Crohn's disease, CHD: coronary heart disease, HT: hypertension, RA: rheumatoid arthritis, T1D: type 1 diabetes and T2D: type 2 diabetes, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-WTCCC1" target="_blank">[42]</a>). The analysis was based on extraction of modified Sidak's minimum <i>P</i>-values <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-Saccone1" target="_blank">[45]</a>, as implemented in LDsnpR. FDR q-value<0.1 was set as cut-off value for significant enrichment.</p>*<p>: One FMCx gene was not represented in the data set.</p>**<p>: Two FMCx genes were not represented in the data set.</p

Gene-based analysis of frontomedial cortex enriched genes for association to cognitive abilities.

<p>The frontomedial cortex enriched genes (n = 29) were analysed for allelic association to nine test measures from the NCNG GWAS: <b>FSIQ</b>: estimated Full-Scale Intelligence Quotient, <b>Vocabulary</b>: Wechsler Abbreviated Scale of Intelligence, Vocabulary, <b>Reasoning</b>: Wechsler Abbreviated Scale of Intelligence, Matrix Reasoning, <b>CVLT-L</b>: California Verbal Learning Test, Learning measure, <b>CVLT-DR</b>: California Verbal Learning Test, Delayed free Recall, <b>Stroop3</b>: the third condition from the D-KEFS Color-Word Interference Test, <b>CDT</b>: Cued Discrimination Task, <b>Valid, Invalid and Neutral</b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-Wechsler1" target="_blank">[37]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-Espeseth1" target="_blank">[40]</a>. The modified Sidak's minimum <i>P</i>-value for each candidate gene was extracted <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-Saccone1" target="_blank">[45]</a>. Only modified Sidak's <i>P</i>-values<0.05 are reported. “-”: non-significant <i>P</i>-value (i.e. <i>P</i>-values>0.05), HGNC: HUGO Gene Nomenclature Committee, SNPs: number of SNPs assigned to each gene by LDsnpR.</p

Schematic overview of the method.

<p>SNP markers from GWAS data were assigned to single genes in a process termed “gene binning”, by implementing a novel LD-based tool (LDsnpR, Christoforou <i>et al.</i> under revision). Modified Sidak's <i>P</i>-values were extracted for each gene (“gene bin”) in the GWAS data sets. Single gene-based analysis of the differentially expressed cortical genes was performed by extracting the modified Sidak's <i>P</i>-values for the candidate genes from the NCNG GWAS. Gene set-based analysis of the differentially expressed cortical genes was performed by extraction of the modified Sidak's <i>P</i>-values, followed by GSEA of GWAS data on cognition, psychiatric disorders and non-psychiatric phenotypes. GSEA: Gene set enrichment analysis, GWAS: Genome-wide association study.</p

Functional characterisation of the human homologues to the rat regionally enriched cortical genes.

<p>Search for over- and under-represented biological processes and molecular functions was performed by using Panther <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-Thomas1" target="_blank">[35]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031687#pone.0031687-Mi1" target="_blank">[36]</a>. The significance of over- and under-represented Panther classification categories in the complete list of candidate genes (i.e. all the cortical regions, column 2), the FMCx enriched genes (column 3), TCx enriched genes (column 4) and OCx enriched genes (column 5), is illustrated by a heat map. The statistical significance of each gene set (negative log <i>P</i>-value) is illustrated by colour intensity (red: over-represented, blue: under-represented, white: as expected). Number of genes in each gene set is listed. The OCx gene <i>HTR5B</i> was not represented in Panther. The percentage of genes within a gene set that map to the given category is indicated on the heat map, e.g. 59% of the 61 enriched genes map to the biological process “cellular process”. The first column states the overall distribution of a term among the 19,911 genes from the default human reference gene list, e.g. 31% of the 61 regional genes were expected to map to ‘“cellular process”, hence this category is significantly over-represented among the regional genes. Exp: expected (based on default human reference gene list), FMCx: frontomedial cortex, TCx: temporal cortex, OCx: occipital cortex, #: number of genes in each gene set, %: percentage of genes.</p