Table 1. DNA methylation probes showing outlier distributions in the affected co-twins from the six adult MZ pairs discordant for depression, and potential neuropsychiatric relevance of their associated genes.
| Probe name (TargetID) | Unadjusted p-value |
Adjusted p-value (q-value) |
β range (%): affected |
β range (%): healthy |
β range difference |
Mean methylation (SD) | Coordinates (hg19) | Gene name (UCSC) |
Gene region feature category (UCSC) |
Brain-blood methylation correlation* | Potential relevance of the gene in neuropsychiatric disorders |
|---|---|---|---|---|---|---|---|---|---|---|---|
| cg00002719 | 9×10−7 | 0.039 | 34.8 | 1.7 | 33.2 | 3.9 | Chr1:169396706 | CCDC181 | TSS200 | None |
CCDC181 methylation has been previously described to be associated with exposure to gestational diabetes mellitus highlighting the importance of prenatal environment in the programming of long-term health and disease [61]. |
| cg00100121 | 3×10−6 | 0.049 | 42.1 | 2.2 | 39.9 | 3.6 | Chr1:169396635 | CCDC181 | 1stExon; 5'UTR |
Cerebellum correlation (p = 0.02) | |
| cg08104202 | 4×10−6 | 0.049 | 35.1 | 2 | 33 | 8.4 | Chr1:169396712 | CCDC181 | TSS200 | None | |
| cg05100739 | 4×10−6 | 0.049 | 15.3 | 1 | 14.4 | 5.7 | Chr17:72733163 | RAB37 | TSS200; 1stExon; Body; TSS200 |
None | Gene expression correlated with brain resting-state oscillatory activity[62]. |
| cg08530065 | 2×10−6 | 0.042 | 22.5 | 1.3 | 21.3 | 86.6 | Chr13:39980228 | LHFP | Body | None | Epigenetic regulation of brain function after prenatal insults[63]. |
| cg10717290 | 3×10−7 | 0.034 | 25.6 | 1 | 24.6 | 9.2 | Chr7:119913576 | KCND2 | TSS200 | Prefrontal cortex (p = 0.03) and cerebellum (p = 0.02) correlations | Suggestive evidence of an etiological role in autism[36]. |
| cg11796442 | 2×10−6 | 0.049 | 35.2 | 1.8 | 33.4 | 17.8 | Chr5:72593919 | - | - | None | - |
| cg12469257 | 3×10−6 | 0.049 | 19.2 | 1.2 | 18 | 88.5 | Chr3:25761040 | NGLY1 | 3'UTR; Body; Body; Body |
None | Association with intellectual disability, neuromotor impairment and neuropathy[64]. |
| cg15240852 | 3×10−6 | 0.049 | 17.2 | 1 | 16.2 | 90.9 | Chr3:131083585 | NUDT16P | Body | None | - |
| cg22058112 | 1×10−6 | 0.041 | 15.9 | 1 | 15.2 | 7.4 | Chr15:42566300 |
TMEM87A; GANC |
TSS1500; TSS200 |
None | - |
| cg22070855 | 8×10−7 | 0.039 | 32.9 | 1.6 | 31.3 | 17.4 | Chr3:172167527 | GHSR | TSS1500 | Prefrontal cortex (p < 0.001), entorhinal cortex (p = 0.02) and superior temporal gyrus (p < 0.001) correlations | Association with substance abuse[65]. Acts as ghrelin receptor, regulating important features in the central nervous system, such as sleep, mood, memory and reward[31]. |
| cg24599017 | 1×10−7 | 0.03 | 14.6 | 0.4 | 14.2 | 96.3 | Chr5:178835885 | - | - | None | - |
| cg24932449 | 4×10−6 | 0.049 | 26.2 | 1.6 | 24.7 | 91.5 | Chr11:2672613 |
KCNQ1; KCNQ1OT1 |
Body; Body |
Prefrontal cortex correlation (p = 0.03) | Putative link with working memory, psychopathology and brain activity[33]. DNA methylation levels at birth may correlate with psychiatric symptoms later in life[35]. |
Note that no SNPs have been described in any of the CpG sites exhibiting outlier distributions. *Brain-blood correlations were retrieved from the Blood Brain DNA Methylation Comparison Tool, a publicly available database [56].
Abbreviations: TargetID, Illumina identifier; 1stExon, first exon; 5’UTR, 5’ untranslated region; Body, within gene body; TSS200, within 200 bp of a TSS.