Table 1.

Summary of Published DNA Methylation Studies on SZ

Reference	Tissue Source	Sample Number	Method	Loci Assessed	Summary of Results
13	Frontal cortex [BA 9 and 10]	5 SZ, 5 controls	MSP and bisulfite sequencing	RELN	SZ-associated hypermethylation at RELN promoter in frontal cortex
14	Frontal cortex [BA 46]	35 SZ, 35 controls	MSP and bisulfite sequencing	COMT	SZ-associated hypomethylation at COMT promoter in tissue samples from left side of brain
	Frontal lobe [BA 9 and 10]	10 SZ, 10 controls
15	Frontal cortex [BA 46]	35 SZ, 35 controls	MSP and bisulfite sequencing	HTR2A	SZ-associated hypermethylation at HTR2A promoter
16	Peripheral blood leukocytes	40 SZ, 67 controls	High-resolution melting assay	5HTR1A	Hypermethylation in SZ
17	Peripheral blood cells	371 SZ, 288 controls	MSP and bisulfite sequencing	MAOA	Significant hypermethylation at individual CpG sites in MAOA promoter in male but not female patients
18	Cerebellum	15 SZ, 15 controls	Pyrosequencing of bisulfite-PCR amplicons	COMT	No significant difference in COMT promoter methylation between SZ and controls
8	Peripheral blood	22 twin pairs discordant for SZ	Illumina 27K HumanMethylation microarray	~27 000 CpG genome-wide sites	Numerous loci with DNA methylation differences between discordant twins
19	Saliva	63 SZ, 76 controls; first-degree relatives: 15 SZ	MSP and bisulfite sequencing	HTR2A	T102C polymorphic site significantly hypomethylated in patients and their first-degree relatives compared to controls
20	Occipital cortex	10 SZ, 10 controls	Direct sequencing of bisulfite-PCR amplicons	RELN	Significant hypermethylation of 4 CpG sites in the RELN promoter in SZ
	Prefrontal cortex [BA 9 and 10]	5 SZ, 5 controls
21	Postmortem prefrontal cortex (BA10)	11 SZ, 12 controls	Clonal sequencing of bisulfite-PCR amplicons	SOX10	SZ-associated hypermethylation and reduced expression of SOX10
22	Whole blood	85 SZ	Pyrosequencing of bisulfite-PCR amplicons	S-COMT	Significant relationship between COMT promoter-region methylation, physical activity, and metabolic syndrome in 158Val/Met patients
23	Peripheral blood leukocytes	177 SZ, 171 controls	Luminometric methylation assay (LUMA)	Global DNA methylation	Significant SZ-associated global hypomethylation in SZ with medication and age effects
			Pyrosequencing of bisulfite-PCR amplicons	S-COMT 5-HTT	S-COMT hypermethylated in SZ
29	Frontal cortex	35 SZ, 35 controls	Enrichment of unmethylated DNA and hybridization to CpG island microarrays	~12 000 CpG genome-wide islands	Significant differences in DNA methylation at multiple loci
24	Saliva	20 SZ, 20 unaffected family members, 25 controls	MSP and bisulfite sequencing	MB-COMT	SZ-associated hypomethylation of MB-COMT promoter
25	Peripheral blood lymphocytes	1 MZ pair concordant, 1 MZ pair discordant	Clonal sequencing of bisulfite-PCR amplicons	DRD2	SZ twin in pair discordant for SZ had DRD2 methylation levels “closer” to the affected concordant twin pair than to its unaffected co-twin
26	Prefrontal cortex [BA 10]	15 SZ, 15 controls	Pyrosequencing of bisulfite-PCR amplicons	RELN	No significant differences
27	Both hemispheres of the superior temporal gyrus, parahippocampus gyrus, and cingulate gyrus	293 SZ, 340 controls	Clonal sequencing of bisulfite-PCR amplicons	FOXP2	Hypermethylation in the left parahippocampus gyrus in SZ patients, opposite patterns in controls
28	Peripheral blood leukocytes	48 same-sex discordant sibling pairs	MSP and direct bisulfite sequencing	DRD2	No significant differences

Note: 5-HTT, 5-hydroxy-tryptamine transporter; BA, Brodmann area; COMT, catechol-O-methyltransferase; DRD2, dopamine D2 receptor; FOXP2, Forkhead box protein P2; HTR1A, 5-hydroxytryptamine (serotonin) receptor 1A; HTR2A, 5-hydroxytryptamine (serotonin) receptor 2A; LUMA, luminometric methylation assay; MAOA, monoamine oxidase A; MSP, methylation-specific PCR; MZ, monozygotic twins; PCR, polymerase chain reaction; RELN, reelin; SOX10, SRY (sex determining region Y)-box 10; SZ, schizophrenia.