Crosstalk analysis of enriched pathways/GO terms.

<p>Panel A shows the connections among the enriched pathways/GO terms. Blue squares are enriched KEGG pathways, green squares are their connected pathways from KEGG, red squares are enriched GO terms. Panel B shows the shared genes between the first group of enriched pathways. Panel C shows the shared genes between four groups of enriched pathways/GO terms. The genes in groups with more than one pathway/GO term were combined for the shared gene analysis.</p

Enriched KEGG pathways and GO terms by module genes.

<p>^a Merged denotes all genes of the merged modules from MGS, Affy6 and Affy500K.</p><p>^b N is total number of genes in the pathway or GO term. X is number of input genes which is mapped to the pathway. Only pathways or GO terms with N < 350 were shown.</p><p>^c FDR is the Benjamini & Hochberg-adjusted <i>P</i>-value. Only pathways or GO terms with FDR < 0.05 were shown.</p><p>CC: cellular component; BP: biological process.</p><p>Enriched KEGG pathways and GO terms by module genes.</p

Protein-protein interaction network involving all merged module genes.

<p>Square nodes denote the reported genes associated with schizophrenia or bipolar disorder. The color of the node was proportioned with the <i>P</i>-value of gene. The width of the edge was proportioned with the No. of repeats of the edge in the modules. The purple edges, green edges and blue edges were interactions from MGS, Affy6 and Affy500K respectively.</p

Crosstalk analysis of enriched pathways/GO terms.

<p>Panel A shows the connections among the enriched pathways/GO terms. Blue squares are enriched KEGG pathways, green squares are their connected pathways from KEGG, red squares are enriched GO terms. Panel B shows the shared genes between the first group of enriched pathways. Panel C shows the shared genes between four groups of enriched pathways/GO terms. The genes in groups with more than one pathway/GO term were combined for the shared gene analysis.</p

Schizophrenia GWAS datasets used for this analysis.

<p>^a The controls of Cardiff UK were from WTCCC [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133404#pone.0133404.ref069" target="_blank">69</a>].</p><p>^b The number of cases, controls and SNPs after quality control were labeled in parentheses.</p><p>Schizophrenia GWAS datasets used for this analysis.</p

Genetic analysis for cognitive flexibility in the trail-making test in attention deficit hyperactivity disorder patients from single nucleotide polymorphism, gene to pathway level

<p><b>Objectives</b>: Investigation of the genetic basis of endophenotype and analysis the pathways with multiple genes of small effects might increase the understanding of the genetic basis of attention deficit hyperactivity disorder (ADHD). Here we aimed to explore the genetic basis of cognitive flexibility in ADHD at the single nucleotide polymorphism (SNP), gene and pathway levels.</p> <p><b>Methods:</b> The trail-making test was used to test the cognitive flexibility of 788 ADHD patients. A genome-wide association analysis of cognitive flexibility was conducted for 644,166 SNPs.</p> <p><b>Results</b>: The top SNP rs2049161 (<i>P</i> = 5.08e-7) involved gene <i>DLGAP1</i> and the top gene <i>CADPS2</i> in the gene-based analysis resulted in much literature evidence of associations with psychiatric disorders. Gene expression and network analysis showed their contribution to cognition function. The interval-enrichment analysis highlighted a potential contribution of ‘adenylate cyclase activity’ and <i>ADCY2</i> to cognitive flexibility. Candidate pathway-based analysis for all SNPs found that glutamate system-, neurite outgrowth- and noradrenergic system-related pathways were significantly associated with cognitive flexibility (FDR <0.05), among which the neurite outgrowth pathway was also associated with ADHD symptoms.</p> <p><b>Conclusions</b>: This study provides evidence for the genes and pathways associated with cognitive flexibility and facilitate the uncovering of the genetic basis of ADHD.</p

Chromatin states of the rs4917129 locus in different cell lines and tissues.

<p>This figure was plotted according to the core-15 states model from the Roadmap Epigenetic project[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0177320#pone.0177320.ref022" target="_blank">22</a>]. The majority of samples used in this analysis were immune-related cell lines or tissues, with several other cell lines or tissues as controls. Chromatin states are denoted with different colors; in particular, yellow indicates an enhancer chromatin state.</p

Data_Sheet_1_A DRD2/ANNK1–COMT Interaction, Consisting of Functional Variants, Confers Risk of Post-traumatic Stress Disorder in Traumatized Chinese.doc

<p>Objective: Post-traumatic stress disorder (PTSD) is a trauma- and stress-related psychiatric syndrome that occurs after exposure to extraordinary stressors. The neurotransmitter dopamine (DA) plays important roles in neurobiological processes like reward and stress, and a link between PTSD and the dopaminergic system has been reported. Thus, the investigation of an association between PTSD and gene–gene interaction (epistasis) within dopaminergic genes could uncover the genetic basis of dopamine-related PTSD symptomatology and contribute to precision medicine.</p><p>Methods: We genotyped seven single nucleotide polymorphisms (SNPs) of three dopaminergic genes DRD2/ANNK1 (rs1800497 and rs1801028), COMT (rs6269, rs4633, rs4818 and rs4680) and DBH (rs1611115), in a Chinese predominantly adult cohort that had been exposed to an earthquake (156 PTSD cases and 978 controls).</p><p>Results: Statistical genetics analysis identified a DRD2/ANNK1–COMT interaction (rs1800497 × rs6269), which is associated with PTSD diagnosis (P_interaction = 0.0008055 and P_corrected = 0.0169155). Single-variant and haplotype-based subset analyses showed that rs1800497 modulates the association directions of both the rs6269 G allele and the rs6269-rs4633-rs4818-rs4680 haplotype G-C-G-G. The interaction (rs1800497 × rs6269) was replicated in a Chinese young female cohort (32 cases and 581 controls, P_interaction = 0.01329).</p><p>Conclusions: Rs1800497 is related to the DA receptor D2 density and rs6269-rs4633-rs4818-rs4680 haplotypes affect the catechol O-methyltransferase level and enzyme activity. Thus, the interaction was inferred to be at protein–protein and DA activity level. The genotype combinations of the two SNPs indicate a potential origin of DA homeostasis abnormalities in PTSD development.</p

Summary of subjects in our study.

<p>Summary of subjects in our study.</p

Protein-protein interaction network for <i>IKZF1</i>.

<p>The edge between the hub and partners indicates the interaction. The networks were drawn using Cytoscape 2.8.2.</p