Table 1. Human Studies of Epigenetics and Neurobehavior.
| Gene(s) Epigenetic change | Major Findings | 1st author & year of publication | ||
|---|---|---|---|---|
| Epigenetics and Neurobehavioral Disease | ||||
| MECP2 DNA methylation | MECP2 promoter hypermethylation in prefrontal cortex of male ASD cases. Lower brain MECP2 expression in ASD cases. | Nagarajan et al 2006 | ||
| MECP2 DNA methylation | Increased methylation of a transition area (upstream of MECP2) in frontal cerebral cortex of male ASD cases. Aberrant MECP2 promoter methylation in ASD female brain. MECP2 methylation is locus-specific rather than global X chromosome changes. | Nagarajan et al 2008 | ||
| OXTR DNA methylation |
OXTR hypermethylation in blood and temporal cortex of ASD cases. Decreased OXTR expression in temporal cortex of ASD cases. |
Gregory et al 2009 | ||
| RORA, BCL-2 DNA methylation | Differentially methylated genes in blood of ASD cases enriched for transcription, nervous system development and cell death/ survival. RORA and BCL-2 exhibited decreased protein expression in tissue arrays (cerebellum and frontal cortex) in ASD cases. 8.1K CpG-island Array (HCGI8.1K) |
Nguyen et al 2010 | ||
| Genome-wide-scan H3K4me3 Histone methylation |
Subset of ASD cases exhibited H3K4me3 spreading into nucleosomes in prefrontal cortex. Identification of 711 loci with altered H3K4me3 signal in brain of ASD cases compared to controls.H3K4me3 peaks enriched in genes implicated in neurodevelopmental disease. Aberrant H3K4 methylation at a specific TSS is a predictor of transcriptional dysregulation. |
Shulha et al 2012 | ||
| EN-2 DNA and histone methylation |
EN-2 promoter hypermethylation in cerebellar cortex associated with ASD, methylation positively correlated with EN-2 expression - Decreased histone H3K27 in the EN-2 promoter in ASD cases. |
James et al 2013 | ||
| PRRT1 TSPAN32/C11orf21 Near ZFP57 SDHAP3 DNA methylation | 3 DMRs Temporal cortex: PRRT1 (3′ UTR) hypomethylation in ASD cases TSPAN32/ C11orf21 hypomethylation in cases Near ZFP57 hypermethylated in cases 1 DMR Cerebellum SDHAP3 hypermethylated in ASD cases |
Ladd-Acosta et al 2013 | ||
| SHANK3 DNA methylation | SHANK3 hypermethylation in cerebellum and cerebral cortex of ASD cases compared to controls. Altered expression an alternative splicing of SHANK3 isoforms in brain tissue. | Zhu et al 2013 | ||
| DRD4 and 5-HTT DNA methylation | Cord blood DNA methylation of DRD4 and 5-HTT regions negatively associated with ADHD symptom score at age 6. | van Mil el al 2014 | ||
| Placental Epigenetics and Newborn Neurobehavior | ||||
| HSD11B2 DNA methylation | Inverse association between placental HSD11B2 methylation and quality of movement scores in RICHS newborns. Pregnancy anxiety and placental HS11B2 methylation (CpG4) interaction influences hypotonicity in RICHS infants |
Marsit et al 2012 Conradt et al 2013 | ||
| NR3C1 DNA methylation | Higher NR3C1 placental promoter methylation associated with higher quality of movement scores and lower infant attention scores in RICHS newborns. Potential interaction between methylation and genotype on infant attention score Pregnancy depression and placental NR3C1 methylation (CpG2) interaction influences self-regulation, hypotonicity, and lethargy in RICHS infants. |
Bromer et al 2012 Conradt et al 2013 |
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| HTR2A DNA methylation | Higher HTR2A placental methylation associated with lower quality of movement and higher infant attention scores in RICHS newborns | Paquette at al 2013 | ||
| LEP DNA methylation | Higher LEP promoter placental methylation associated with membership in a NNNS neurobehavioral profile marked by increased lethargy and hypotonicity and reduced risk of membership in a profile with opposite characteristics in RICHS newborns. | Lesseur et al 2014 | ||
| Expression of 22 imprinted genes | Placental imprinted gene expression classes associated with quality of movement and handling in RICHS newborns. | Marsit et al 2012 | ||
| Expression of 6 placental miRNAs | Increased miR-16 placental expression associated with reduced attention, Increased miR-146a and miR-182 placental expression associated with increased quality of movement in RICHS newborns. | Maccani et al 2013 | ||
ASD, autism spectrum disorder; MECP2, methyl CpG binding protein 2; OXTR, oxytocin receptor; RORA, RAR-related orphan receptor A; BCL-2, B-cell CLL/lymphoma 2; H3K4me3, trimethylation of lysine 4 of histone 3; EN-2, engrailed homeobox 2; DMR, differentially methylated region; PRRT1, proline-rich transmembrane protein 1; TSPAN32, tetraspanin 32; C11orf21, chromosome 11 open reading frame 21; ZFP57, zinc finger protein; SDHAP3, succinate dehydrogenase complex, subunit A, flavoprotein pseudogene 3; SHANK3, SH3 and multiple ankyrin repeat domains 3; DRD4, dopamine receptor D4; SLC6A4 solute carrier family 6; HSD11B2, hydroxysteroid (11-beta) dehydrogenase 2; NR3C1, glucocorticoid receptor; HTR2A 5-hydroxytryptamine (serotonin) receptor 2A; LEP, leptin.