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Epigenetic Epidemiology of Autism and Other Neurodevelopmental Disorders

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Epigenetic Epidemiology

Abstract

The prevalence of neurodevelopmental disorders (NDD) has been rising gradually over the last two decades. These developmental disabilities are caused by genetic and environmental factors, reciprocally. Recent extensive epigenetic epidemiological studies suggest that epigenetic dysregulations (Epimutation) such as abnormal DNA methylation may contribute to the etiology of NDD including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID). Epimutations of DNA methylation and histone modification have been found in genetic loci under epigenetic regulation but also allele- or tissue-specific patterns in individuals with NDD. Epigenetic reprograming and remodeling occur from embryonic development to throughout life. Recent technical advances in epigenome-wide association studies (EGWAS) and genome-wide differentially methylated regions (DMRs) analyses have established correlations between abnormal DNA methylation and histone modification and neurodevelopmental dysfunctions. However, it remains a challenge to establish a concrete causative evidence that is implicated in the pathogenesis of NDD.

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Abbreviations

5caC:

5-carboxylcytosine

5fC:

5-formylcytosine

5hmC:

5-hydroxymethylcytosine

5mC:

5-methylcytosine

ADHD:

Attention-deficit/hyperactivity disorder

ASD:

Autism spectrum disorder

CDC:

Centers for Disease Control and Prevention

CHD:

Chromodomain helicase DNA binding protein

ChIP-seq:

Chromatin immunoprecipitation sequencing

CNVs:

Copy number variants

CpG:

CG dinucleotides

DA:

Differential acetylation

DhMRs:

Differentially hydroxymethylated regions

DMRs:

Differentially methylated regions

DNMT:

DNA methyltransferase

EWAS:

Epigenome-wide association studies

GWAS:

Genome-wide associated study

HAWAS:

Histone acetylome-wide association study

ID:

Intellectual disabilities

IQ:

Intelligence quotient

KAT:

lysine acetyltransferase

KDM:

lysine demethylase

KMT:

lysine methyltransferase

NDD:

Neurodevelopmental disorders

NGS:

Next generation sequencing

PFC:

Prefrontal cortex

PTVs:

Protein-truncating variants

SAM:

S-adenylsylmethionine

SCZ:

Schizophrenia

SNP:

Single nucleotide polymorphism

SNVs:

Single nucleotide variants

TC:

Temporal cortex

TET:

Ten-eleven translocation

TSS:

transcription start sites

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  1. Department of Genetics, Yale University School of Medicine, New Haven, CT, USA

    Sung Eun Wang & Yong-Hui Jiang

  2. Department of Neuroscience and Pediatrics, Yale University School of Medicine, New Haven, CT, USA

    Yong-Hui Jiang

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  1. Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, USA

    Karin B. Michels

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Wang, S.E., Jiang, YH. (2022). Epigenetic Epidemiology of Autism and Other Neurodevelopmental Disorders. In: Michels, K.B. (eds) Epigenetic Epidemiology. Springer, Cham. https://doi.org/10.1007/978-3-030-94475-9_17

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