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

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)