From: DNA methylation in peripheral tissue of schizophrenia and bipolar disorder: a systematic review
Ref. | N | Mean age (SD) | Sex (FÂ %) | Method | Subgroup analyses /covariates | RESULTS: methylation loci | |||
---|---|---|---|---|---|---|---|---|---|
 | SZ | HC | SZ | HC | SZ | HC |  |  |  |
Aberg et al., 2014 [20] | 759 | 738 | 53 (12) | 55 (12) | 45 | 46 | MBD protein-enriched genome sequencing b, d, e | Age, sex, smoking m, alcohol use m, medication m, autoimmune disorders m | Differential methylation l of FAM63B, RELN (first intron), FCAR and 8 other genes linked to hypoxia & the immune system |
Aberg et al., 2012 [21] | 750 | 750 | - | - | - | - | MBD protein-enriched genome sequencing b, d, i | Age, sex | Differential methylationl of GRIA2, HTRA3, CAMK2D, FNDC3B and DCTN |
Bonsch et al., 2012 [22] | 27 | 34 | - | - | 30 | 47 | Modified non-radioactive elongation assay and MSRE-quantitative PCR a, c, d, e | Sex k, medication j, promoter methylation compared to global DNA methylation | Global methylation differences l; Lower methylation of RELN and SOX10 promoters c, m in SZ; SZ on medication had similar methylation levels to HC |
Bromberg et al., [23] | 28 | 26 | 39 (14) | 42 (10) | 64 | 62 | Radiolabelled [3H] cytosine-extension assay a, d, e | Age m, sex, smoking l, illness duration m, medication m | No global methylation differences m; Higher methylation in SZ non-smokers |
Chen et al., 2012 [24] | 371 | 288 | - | - | 46 | 57 | Bisulfite sequencing c, d, e | Sex j | No differential methylation of MAOA (promoter) m Greater methylation in SZ females compared to males |
Ikegame et al., 2013 [25] | 100 | 100 | 43 (13) | 46 (12) | 46 | 45 | Pyrosequencing c, d, e | Age m, sex j | Hypermethylation of BDNF (promoter I) j for SZ CpG-72 compared HC, however methylation generally low in SZ/HC; No diffferential methylation of BDNF (promoter IV) m between groups; higher methylation in SZ/HC females at all CpG sites |
Kinoshita et al., 2014 [26] | 63 | 42 | 49 (10) | 47 (10) | 22 | 40 | 450Â K methylation array a, d, f | Age, sex, cell type heterogeneity l | Global methylation differences (485 764 CpG sites) l Hypermethylation in SZ found in 1161 CpG sites when controlling for cellular heterogeniety |
Kinoshita et al., 2013a [27] | 42 | 42 | 52 (7) | 52 (6) | 0 | 0 | 450Â K methylation array a, d, e | Age, medication | Global methylation differences (164 657 CpG sites) l including SLC18A2, GNAL, KCNH2 and NTNG2 |
Kinoshita et al., 2013b [28] | 24 | 23 | 31 (11) | 31 (10) | 54 | 57 | 450Â K methylation array a, d, e | Sex l | Global methylation differences in SZ (485 764 CpG sites) l including B3GAT2, HDAC4, DGKI, PCM1, INSIG2, GFRA2 and RAI1; Did not replicate published methylation findings in SZ for COMT, HTA1A and MAOA |
Kordi-Tamandani et al., 2013a [29] | 81 | 71 | 48 (11) | 47 (12) | 25 | 20 | Methylation specific PCR c, d, g | - | Hypermethylation of GMR2 j, GMR5 j, GRIA3 j, GMR8 j (all promoter regions) |
Kordi-Tamandani et al., 2012 [30] | 80 | 71 | 48 (11) | 47 (12) | - | - | Methylation specific PCR c, d, g | - | Differential methylation of BDNF (promoter) l and DAT1 j |
Kordi-Tamandani et al., 2013b [31] | 94 | 99 | 48 (11) | 47 (12) | 29 | 27 | Methylation specific PCR c, d, g | Genotype m | Hypermethylation of CTLA4 (promoter) j increased in SZ |
Liao et al., 2014 [32] | 2 | 1 | 25 (4) | 31 (0) | 100 | 100 | MBD protein-enriched genome sequencing a, c, d, h | Paranoid j/undifferentiated illness type l | Global methylation differences l; GRB2 j, PRKCA j, DLG4 j, MAPT-S1 j, DISC1 j and 16 other genes; Differential methylation mostly found in intergenic and intronic regions |
Liu et al., 2013 [33] | 98 | 108 | 34 (11) | - | 25 | 36 | 27Â K methylation assay a, d, f | Age, sex, ethnicity, alcohol/nicotine/cannabis use, SZ symptoms l, medication j, illness duration j, age of onset l | Global methylation differences (7562 CpG sites) in SZ l: MS4A1 j, MPG k, SLC25A10 j, CBFA2T3 k and 17 other genes l linked to inflammatory response, haematological development and cytotoxic reactions; Hypermethylation of MS4A1 associated with chlorpromazine dosage; Higher methylation of MPG and SLC25A10 associated with longer illness duration; Hypomethylation of CBFA2T3 associated with age of SZ onset |
Melas et al., 2012 [34] | 177 | 171 | 52 (9) | - | 51 | - | Luminometric methylation assay and bisulfite sequencing a, c, d, e | Age m, sex m, smoking m, alcohol use m, medication (haloperidol) l, hospital admissions m, length of hospital stay m, familial absence of SZ m, age of onset k | Global methylation differences in SZ l ; No differential methylation of 5-HTT (8 CpG sites) m; hypermethylation of S-COMT (5 CpG sites) j |
Murphy et al., 2008 [35] | 18 | 31 | - | - | - | - | Bisulfite sequencing c, d, e | - | No differential methylation of SYNIII m |
Murphy et al., 2005 [36] | 20 | 31 | - | - | - | - | Bisulfite sequencing c, d, i | - | No differential methylation of S-COMT (promoter) m |
Nishioka et al., 2013 [37] | 17 | 15 | 23 (5) | 23 (4) | 59 | 33 | 27Â K methylation assay a, d, f | Sex m, SZ symptoms, GAF score, duration of untreated psychosis, age at onset | Global methylation differences (603 CpG sites)Â in SZ l : COMTD1 (promoter) l, SLC6A3 k, HTR1E l and 7 other genes l related to the nuclear lumen, transcription factor binding and nucleotide binding |
Ota et al., 2014 [38] | 51 | 51 | 25 (8) | 26 (8) | 37 | 37 | Bisulfite sequencing c, d, i | Age m, sex j | Hypermethylation of GCH1 j (CpG13, CpG15, CpG16 and CpG21 only) in first episode psychosis; Only CpG21 j in SZ males |
Pun et al., 2011 [39] | 30 | 30 | - | - | 50 | 37 | Bisulfite sequencing c, d, e | Single-nucleotide polymorphism | Hypermethylation of GABRB2 in SZ (CpG sites 1–26) j |
Shimabukuro et al., 2007 [40] | 210 | 237 | - | - | 41 | 54 | HPLC a, d, f | Age l, sex k, subtypes of SZ m | Global hypomethylation in SZ k In SZ males hypomethylation decreases with age |
Van Eijk et al., 2014 [41] | 264 | 252 | - | - | - | - | 27Â K methylation assay a, d, f | Age, sex, gene expression associations l | Global methylation differences (11 320 CpG sites)in SZ l: including PRRT1, HLA-C, MRPL41, CALHM1; Significant association between DNA methylation and gene expression |