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Table 7 Comparisons of study features investigating DNA methylation across the genome of ME/CFS patients compared to controls

From: Changes in DNA methylation profiles of myalgic encephalomyelitis/chronic fatigue syndrome patients reflect systemic dysfunctions

Study Tissue Method Cohort Diagnostic criteria Statistical thresholds No. of significant differences
NZ PBMCs Reduced representation bisulphite sequencing P = 10
5 females
5 males
C = 10
5 females
5 males
Canadian criteria DMAP ANOVA F test Raw P < 0.05, methylation diff ± 15%
MethylKit Fisher’s exact test FDR corrected P < 0.05. methylation diff ± 15%
DMAP: 76 (52% hypo-methylated)
Methylkit: 394 (56% hypo-methylated)
A CD4 + T cells Infinium HumanMethylation450 BeadChip P = 25
21 females
4 males
C = 18
10 females
8 males
Fukuda criteria Raw P value < 0.05, methylation fold change > 2.0 120 (85% hypo-methylated)
B PBMCs Infinium HumanMethylation450 BeadChip P = 12, C = 12
All female
Fukuda and Canadian criteria Wilcoxon-rank sum test P < 0.05, FDR corrected P < 0.05 (Benjamini-Hochberg). Mean beta difference > 0.20 1192 (72% hyper-methylated)
C PBMCs Infinium HumanMethylation450 BeadChip P = 49, C = 25
All female
Fukuda and Canadian criteria Wilcoxon-rank sum test P < 0.05, FDR corrected P < 0.05. Mean beta difference > 0.05 12,608 (71.6% hyper-methylated)
D* PBMCs Illumina Methylation EPIC microarray P = 13, C = 12
All female
Fukuda and Canadian criteria FDR-corrected P value < 0.05 absolute beta difference > 0.05 17,296 (98% hypo-methylated)
E CD3 + T Cells Infinium HumanMethylation450 BeadChip P = 43
34 females
9 males
C = 36
27 females
9 males)
Fukuda and Canadian criteria P value < 0.05 permutation analysis, mean percentage methylation difference > 5% 133 (74% hyper-methylated)
  1. A table comparing the NZ study with the five previous studies investigating DNA methylation in ME/CFS patients vs. controls. (NZ = this study, A = Brenu et al. 2014 [6], B = de Vega et al. 2014 [7], C = de Vega et al. 2017 [8], D = Trivedi et al. 2018 [9], E = Herrera et al. 2018 [10]) The table includes the cell type utilised, the method used in the analysis, the numbers and gender included in the cohort, diagnostic criteria of the patients and the statistical thresholds utilised in the analyses. *D (Trivedi et al. [9]) included a larger cohort for pyrosequencing validation with a total of 33 cases and 31 controls from three geographical locations