Seed Voxel Localization.

<p>Top: Frequencies of MNI-coordinates in the X, Y, and Z dimension for right DLPFC seed regions identified with the global maximum and the next local maximum starting at 52, 30, 30. Bottom: Individual seed-region localization in the right DLPFC for the functional connectivity analyses based on the global maximum (left) and the next local maximum approach (right).</p

Influence of Noise Regression Methods on Connectivity Patterns.

<p>Functional connectivity group results (using one sample t-tests) with respect to the right DLPFC for the “standard implementation” of the connectivity analysis (top) and the additional global signal correction by application of the global normalization procedure (bottom). Yellow-red: positive correlations with seed voxel, green-blue: negative correlations with seed voxel.</p

Influence of Noise Regression Methods on the Comparisons of Genetic Groups.

<p>A linear increase with with rs1006737 genotype in functional coupling between the right DLPFC (seed voxel) and the right hippocampus is detected for both noise reduction algorithms. However, the interpretation of the changes depending on the underlying correlation profile. While in the “standard implementation” one would argue that the hippocampus is decoupled in GG carriers and that coupling increases with genetic risk (GG</p

Sample characteristics: sex, age and education. According to their rs1006737 genotype subjects were divided into three groups (G/G, G/A, and A/A). G = Guanine, A = Adenine (risk allele).

<p>Sample characteristics: sex, age and education. According to their rs1006737 genotype subjects were divided into three groups (G/G, G/A, and A/A). G = Guanine, A = Adenine (risk allele).</p

Influence of Seed Voxel Coordinates as Covariates on the Group Level.

<p>Reduction of genotype effects after entering seed-voxel localization as covariate on the second level. Left: A linear decrease in regional activation is found with number rs1006737 risk alleles in the right DLPFC (blue). A similar gene-dosage dependent effect in functional connectivity was found at the same location (red). After controlling for differences in the spatial distribution of seed-voxel localization with introduction of the MNI coordinates in the x-, y-, and z-dimension as covariate on the second level the associations of genotype with DLPFC connectivity was reduced and non-significant at p>.05 corrected</p

Influence of Seed Voxel Localization on the Comparisons of Genetic Groups.

<p>Left: Interaction between the factors method (next local maximum vs. global maximum) and rs1006737 genotype (G/G, G/A, A/A) in the left anterior HF. Right: A post-hoc analysis of the parameter estimates of each risk group separately for both methods. A significant linear gene-dosage effect is found only with one method of seed region selection, the next local maximum approach.</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

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