TE: treatment effect (i.e., the mean difference between cases and controls); seTE: standard error of the treatment effect.
With the exception of the IoPPN and EUGEI cohorts, there is little ethnic heterogeneity in each of the cohorts with samples being predominantly of Caucasian origin.
DNAmAge was calculated using the algorithm described by Horvath, 2013. Each point represents an individual and is colored by psychosis status (blue = psychosis, red = control). The solid diagonal …
PhenoAge was calculated using the algorithm described by Levine et al., 2018. Each point represents an individual and is colored by psychosis status (blue = psychosis, red = control). The solid …
DNAmAge was calculated using the algorithm described by Horvath, 2013. Each point represents an individual and is colored by medication status (yellow = schizophrenia cases not prescribed clozapine, …
PhenoAge was calculated using the algorithm described by Levine et al., 2018. Each point represents an individual and is colored by schizophrenia status (yellow = schizophrenia cases not prescribed …
Shown are forest plots from meta-analyses of differences in blood cell proportions derived from DNA methylation data between psychosis patients and controls for (A) monocytes, (B) granulocytes, (C) …
Shown are forest plots from meta-analyses of differences in estimated blood cell proportions derived from DNA methylation data between treatment-resistant schizophrenia patients prescribed clozapine …
Shown are forest plots from meta-analyses of differences in estimated granulocyte proportions derived from DNA methylation data between (A) schizophrenia patients and controls and (B) …
Shown are forest plots from meta-analyses of differences in estimated granulocyte proportions derived from DNA methylation data between (A) schizophrenia patients and controls and (B) …
Forest plot from a meta-analysis of differences in smoking score derived from DNA methylation data between psychosis patients and controls. The smoking score was calculated from DNA methylation data …
Shown is the DNA methylation smoking score (y-axis) from individuals in the IoPPN cohort for whom self-reported smoking data was available regarding current (left panel) and former (right panel) …
Forest plot from meta-analyses of differences in smoking derived from DNA methylation data between treatment-resistant schizophrenia patients prescribed clozapine and schizophrenia patients …
(A) Schizophrenia diagnosis was associated with a significant increase in smoking score (mean difference = 3.98; p=2.19×10-8) with (B) TRS status associated with an additional increase within cases …
Manhattan plots depicting the –log10 p-value from the epigenome-wide association study meta-analysis (y-axis) against genomic location (x-axis). (A) presents results from the analysis comparing …
Shown is a scatterplot of statistics (–log10 p-value) from an epigenome-wide association study (EWAS) of psychosis in the IoPPN cohort without the inclusion of any genetic PCs in the analysis model …
Shown are forest plots for differentially methylated positions (DMPs) annotated to the GABA transporter SLC6A12 (cg00517261; p=1.53×10−8), the GABA receptor GABBR1 (cg00667298; p=5.07×10−9), and the …
Shown for each overlapping DMP is the association effect size for the other trait (x-axis) taken from the online EWAS catalog (http://ewascatalog.org/) compared to the effect size identified in our …
A series of density plots for estimates of additive genetic effects (A, left), common environmental effects (C, middle), and non-shared environmental effects (E, right) derived using data from a …
Forest plots from a meta-analysis of differences in DNA methylation at cg16322565 located in the NR1L2 gene on chromosome 3 between (A) schizophrenia patients and controls and (B) TRS patients …
TE: treatment effect (i.e., the mean difference between cases and controls); seTE: standard error of the treatment effect.
TE: treatment effect (i.e., the mean difference between cases and controls); seTE: standard error of the treatment effect.
Shown is the mean difference (% DNAm) between cases and controls.
Shown is a histogram of –log10(p-values) for the interaction term between age and schizophrenia status across all 1,048 SZ-associated DMPs.
Shown is a histogram of –log10(p-values) for the interaction term between sex and schizophrenia status across all 1,048 SZ-associated DMPs.
Overall there is a significant enrichment of consistent results between the analyses for these DMPs. The red crosses highlight the two DNAm sites that were reported as significant by Montano et al. …
Overall there is a significant enrichment of consistent results between the analyses for SZ-associated DMPs. Black dots represent DMPs that we found to show low covariation (r < 0.2) between blood …
Cohort | UCL | Aberdeen | Twins | IoPPN | Dublin | EU-GEI | Sweden | Total | |
---|---|---|---|---|---|---|---|---|---|
Total sample | 675 | 847 | 192 | 800 | 679 | 912 | 378 | 4483 | |
% Cases | 52.3 | 48.9 | 45.3 | 74.6 | 51.3 | 42.9 | 50.0 | 53.1 | |
% Schizophrenia | 52.3 | 48.9 | 45.3 | 36.3 | 51.3 | 0.0 | 50.0 | 37.5 | |
% First-episode psychosis | 0.0 | 0.0 | 0.0 | 38.4 | 0.0 | 42.9 | 0.0 | 15.6 | |
% Males | All | 58.7 | 71.1 | 52.1 | 63.0 | 71.0 | 54.4 | 59.5 | 62.6 |
Cases | 72.0 | 68.4 | 54.0 | 65.3 | 71.6 | 64.2 | 60.3 | 66.8 | |
Controls | 44.1 | 73.7 | 50.5 | 56.2 | 70.4 | 47.0 | 58.7 | 57.8 | |
Chi-square test p-value | 3.81E-13 | 0.103 | 0.730 | 0.024 | 0.804 | 3.68E-07 | 0.834 | 9.35E-10 | |
Age (years) | Mean | 40.4 | 44.6 | 35.3 | 28.8 | 41.7 | 35.3 | 60.0 | 40.5 |
SD | 15.0 | 12.9 | 10.8 | 9.46 | 12.0 | 12.8 | 8.86 | 14.7 | |
Mean in controls | 43.7 | 44.2 | 37.9 | 27.8 | 41.4 | 30.7 | 56.3 | 41.6 | |
Mean in cases | 36.8 | 44.9 | 33.3 | 30.3 | 42.0 | 38.7 | 63.7 | 39.4 | |
t-test p-value | 6.55E-09 | 0.529 | 0.033 | 0.007 | 0.505 | 1.24E-22 | 1.05E-16 |
Cell type | Measure type | Number of cohorts | Random effects model | Fixed effects model | Heterogeneity p-Value | ||||
---|---|---|---|---|---|---|---|---|---|
Mean difference | SE | p-Value | Mean difference | SE | p-Value | ||||
Monocytes | Proportion | 7 | 0.00320 | 0.00083 | 0.000115 | 0.00320 | 0.00083 | 0.000115 | 0.6490 |
Granulocytes | Proportion | 7 | 0.04312 | 0.01241 | 0.000509 | 0.03930 | 0.00315 | 1.21E-35 | 2.22E-16 |
Natural killer cells | Proportion | 7 | −0.01135 | 0.00385 | 0.003221 | −0.00827 | 0.00133 | 4.48E-10 | 2.43E-08 |
CD4+ T-cells | Proportion | 7 | −0.01767 | 0.00555 | 0.00144 | −0.01569 | 0.00196 | 1.15E-15 | 1.23E-07 |
CD8+ T-cells | Proportion | 7 | −0.01444 | 0.00457 | 0.001586 | −0.01443 | 0.00148 | 1.31E-22 | 8.13E-10 |
B-cells | Proportion | 7 | −0.00495 | 0.00280 | 0.077103 | −0.00477 | 0.00102 | 2.75E-06 | 2.25E-07 |
PlasmaBlast | Abundance | 5 | 0.05626 | 0.02987 | 0.059671 | 0.05332 | 0.00722 | 1.55E-13 | 8.45E-13 |
CD8pCD28nCD45RAn | Abundance | 5 | 0.06280 | 0.22674 | 0.781792 | 0.10797 | 0.14981 | 0.4711 | 0.0826 |
CD8 naive T-cells | Abundance | 5 | 7.21687 | 3.12594 | 0.02096 | 8.03957 | 1.89169 | 2.14E-05 | 0.0443 |
CD4 naive T-cells | Abundance | 5 | 11.77240 | 4.72532 | 0.012726 | 11.77240 | 4.72532 | 0.0127 | 0.824 |
Shown are traits with more than one overlapping DMP.
Trait | Total Overlap | Discordant direction of effect | Concordant direction of effect | P-value |
---|---|---|---|---|
Age | 30 | 28 | 2 | 8.68E-07 |
Alcohol consumption per day | 8 | 7 | 1 | 0.070313 |
Body mass index | 11 | 0 | 8 | 0.007813 |
C-reactive protein | 10 | 0 | 10 | 0.001953 |
Gestational age | 105 | 33 | 72 | 0.000178 |
HIV infection | 8 | 4 | 4 | 1 |
Inflammatory bowel disease | 2 | 0 | 0 | NA |
Maternal smoking in pregnancy | 7 | 2 | 5 | 0.453125 |
Primary Sjogrens syndrome | 31 | 0 | 0 | NA |
Rheumatoid arthritis | 20 | 14 | 6 | 0.115318 |
Serum high-density lipoprotein cholesterol | 12 | 12 | 0 | 0.000488 |
Serum low-density lipoprotein cholesterol | 2 | 0 | 2 | 0.5 |
Serum total cholesterol | 5 | 0 | 5 | 0.0625 |
Sex | 54 | 0 | 1 | 1 |
Smoking | 16 | 4 | 1 | 0.375 |
Shown are traits with more than one overlapping DMP
Trait | Total Overlap | Discordant direction of effect | Concordant direction of effect | P-value |
---|---|---|---|---|
Age | 3 | 3 | 0 | 0.25 |
Body mass index | 4 | 3 | 0 | 0.25 |
C-reactive protein | 5 | 1 | 4 | 0.375 |
Gestational age | 20 | 9 | 11 | 0.823803 |
HIV infection | 3 | 2 | 1 | 1 |
Primary Sjogrens syndrome | 3 | 0 | 0 | NA |
Rheumatoid arthritis | 4 | 0 | 4 | 0.125 |
Sex | 19 | 0 | 1 | 1 |
Smoking | 6 | 3 | 0 | 0.25 |
Supplementary Tables 1-14.