Gene ontology results of significantly enriched GO terms identified in a combined analysis of DNA methylation and gene expression in CD4⁺ cells.

a<p>Number of genes in the given input gene list which are involved in a specific GO term.</p>b<p>Percentage of the genes in the given input gene list which are involved in a specific GO term.</p>c<p>Adjusted according to Benjamini and Hochberg.</p

Subset of genes with a correlated difference in DNA methylation and gene expression.

<p>This table consists of the top 50 genes ranked according to the significance of the correlation of differences in DNA methylation and gene expression between unaffected and affected MZ co-twins in CD4⁺ cells (genes known to be associated with psoriasis are shown in bold). The magnitude of the mean differences in DNA methylation and gene expression (unaffected versus affected) are presented as deltaBeta and log fold change, respectively.</p

Volcano plots of cell-type specific differences in DNA methylation and gene expression.

<p>(A) Differences in DNA methylation between CD4⁺ and CD8⁺ cells. Each point represents a CpG site, with mean β-value difference across 12 unaffected individuals along the <i>x</i>-axis and −log10 of a corrected <i>P</i>-value from a paired <i>t</i>-test along the <i>y</i>-axis. (B) Differences in gene expression between CD4⁺ and CD8⁺ cells. Each point represents a gene, with mean log2 fold change across 13 unaffected individuals along the <i>x</i>-axis and −log10 of a corrected <i>P</i>-value from a paired <i>t</i>-test along the <i>y</i>-axis. Dashed lines represent the FDR of 5%.</p

Volcano plots of differences in DNA methylation and gene expression in discordant MZ twins.

<p>(A–B) Differences in DNA methylation in CD4⁺ (<i>n</i> = 17 pairs) and CD8⁺ cells (<i>n</i> = 13 pairs), respectively. Each point represents a gene, with mean co-twin β-value difference along the <i>x</i>-axis and −log10 of the uncorrected <i>P</i>-value from a paired <i>t</i>-test along the <i>y</i>-axis. (C–D) Differences in gene expression in CD4⁺ cells (<i>n</i> = 17 pairs) and CD8⁺ cells (<i>n</i> = 14 pairs), respectively. Each point represents a gene, with mean log2 fold change along the <i>x</i>-axis and log odds along the <i>y</i>-axis.</p

Bipolar disorder polygenic risk score is positively correlated with BOLD activation in the right inferior frontal gyrus in the entire sample (N = 206) including bipolar disorder cases and healthy controls for the Negative Faces > Shapes contrast.

<p>Color bar indicates z values. Coordinates are given in MNI space. Y = 18 (coronal view), Z = 12 (transversal view). Abbreviations: R, right; A, anterior.</p

Demographic data and clinical characterization of individuals participating in a faces matching functional MRI study.

<p>Abbreviations: BD, bipolar disorder; HC, healthy controls; SD, standard deviation; WASI, Wechsler Abbreviated Scale of Intelligence; IDS, Inventory of Depressive Symptoms; YMRS, Young Mania Rating Scale; PANSS P score, Positive and Negative Syndrome Scale positive subscale; GAF-S, Global Assessment of Functioning–symptom score; GAF-F, Global Assessment of Functioning–function score; BD PGRS, bipolar disorder polygenic risk score; ms, milliseconds.</p><p>BD PGRS values are reported as z-scores (with SD in brackets).</p><p>Complete behavioral data (response times and accuracy rates per condition) were available for 80/85 BD and 119/121 HC. For the remaining individuals (5 BD, 2 HC), an accuracy rate for each session (i.e. a combined rate for negative faces and shapes, and for positive faces and shapes) was available and was used to confirm that the participants paid attention to the task (accuracy rate: 97.4% and 96.0%, respectively).</p><p>^a Mean age at fMRI scanning. Age range was 18 to 63.</p><p>^b IDS score at scanning was available for 60/85 individuals (70.6%).</p><p>^c YMRS score at scanning was available for 69/85 individuals (81.2%).</p><p>^d PANSS P score at scanning was available for 38/85 individuals (44.7%).</p><p>^e Last six months</p><p>Demographic data and clinical characterization of individuals participating in a faces matching functional MRI study.</p

Decreased brain activation in cuneus/precuneus in bipolar disorder cases (N = 85) compared to healthy controls (N = 121) for the Negative Faces > Shapes contrast.

<p>Color bar indicates z values. Coordinates are given in MNI space. X = 4 (sagittal view), Z = 22 (transversal view). Abbreviations: R, right; A, anterior.</p

Significant clusters at whole-brain level for diagnostic category and polygenic risk score analyses, corrected for sex and age.

<p>*Remains significant after Bonferroni correction (8 independent tests)</p><p>^#P < 0.05 with IQ and education in model</p><p>Abbrevations: Pos, Positive; Neg, Negative; HC, healthy controls; BD, bipolar disorder; PGRS, polygenic risk score; L, left; R, right. ‘+’, positively associated; ‘-’, negatively associated.</p><p>Coordinates are given in MNS space.</p><p>Significant clusters at whole-brain level for diagnostic category and polygenic risk score analyses, corrected for sex and age.</p

Stratified Q–Q plot and Stratified True Discovery Rate plots.

<p><i>Upper panel:</i> Stratified Q-Q plot of nominal versus empirical −log₁₀ p-values (corrected for inflation) in A) schizophrenia (SCZ) below the standard GWAS threshold of p<5×10⁻⁸ as a function of significance of the association with bipolar disorder (BD) at the level of −log₁₀(p)>0, −log₁₀(p)>1, −log₁₀(p)>2, −log₁₀(p)>3 corresponding to p<1, p<0.1, p<0.01, p<0.001, respectively, and in B) BD below the standard GWAS threshold of p<5×10⁻⁸ as a function of significance of association with SCZ at the level of −log₁₀(p)>0, −log₁₀(p)>1, −log₁₀(p)>2, −log₁₀(p)>3 corresponding to p<1, p<0.1, p<0.01, p<0.001, respectively. Dotted lines indicate the null-hypothesis. <i>Lower panel:</i> Stratified True Discovery Rate (TDR) plots illustrating the increase in TDR associated with increased pleiotropic enrichment in C) SCZ conditional on nominal BD p-values (SCZ|BD), and D) BD conditional on nominal SCZ p-values (BD|SCZ). For more information about QQ plots, see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003455#pgen.1003455.s009" target="_blank">Text S1</a>.</p

‘Conjunctional FDR Manhattan plot’ of conjunctional (FDR<0.05) values for triglycerides.

<p>Conjunctional—log₁₀(FDR) values for triglycerides (TG) and Crohn’s Disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), psoriasis (PSOR) and G) sarcoidosis (SARC) were plotted along their chromosome locations. SNPs with conjunctional FDR < 0.05 (i.e.,—log₁₀ FDR > 1.3) are shown with enlarged data points. A black circle around the enlarged data points indicates the most significant SNP in each LD block and this SNP was annotated with the closest gene which is listed above the symbols in each locus, except for the Major Histocompatibility Complex (MHC) region on chromosome 6. The figure shows the localization of 88 TG loci. Details for the associated loci outside of chromosome 6 are shown in Table E in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123057#pone.0123057.s001" target="_blank">S1 File</a>.</p