Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits
Open accessAbstract
Autism spectrum disorder (ASD) defines a group of common, complex neurodevelopmental disorders. Although the aetiology of ASD has a strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating a role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant MZ twin pairs provide an ideal model for examining the contribution of environmentally driven epigenetic factors in disease. We performed a genome-wide analysis of DNA methylation in a sample of 50 MZ twin pairs (100 individuals) sampled from a representative population cohort that included twins discordant and concordant for ASD, ASD-associated traits and no autistic phenotype. Within-twin and between-group analyses identified numerous differentially methylated regions associated with ASD. In addition, we report significant correlations between DNA methylation and quantitatively measured autistic trait scores across our sample cohort. This study represents the first systematic epigenomic analyses of MZ twins discordant for ASD and implicates a role for altered DNA methylation in autism.
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In humans, epigenetic mechanisms implicated in ASD may be a key mechanism through which valproate influences neurodevelopment.
“In humans epigenetic mechanisms implicated in ASD may be a key mechanism through which valproate influences neurodevelopment [34–37].”
From The contribution of environmental exposure to the etiology of autism spectrum disorder (2019) · cites this paper as [36]
Among 50 pairs of disease discordant monozygotic twins, several genes were found to be differentially methylated between the twin diagnosed with ASD and the nonsymptomatic twin, including genes previously implicated in ASD pathology such as GABRB3, AFF2, NLGN2, JMJD1C, SNRPN, SNURF, UBE3A, and KCNJ10.
“Among 50 pairs of disease discordant monozygotic twins, several genes were found to be differentially methylated between the twin diagnosed with ASD and the nonsymptomatic twin, including genes previously implicated in ASD pathology such as GABRB3 , AFF2 , NLGN2 , JMJD1C , SNRPN , SNURF , UBE3A, and KCNJ10 [ 21 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [21]
There were significant DNA methylation differences between autistic twin pairs discordant for autistic traits (social, restrictive repetitive behaviors and interests, and communication).
“Further, there were significant DNA methylation differences between autistic twin pairs discordant for autistic traits (social, restrictive repetitive behaviors and interests, and communication) [ 21 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [21]
Changes in DNA methylation at differentially methylated CpG sites correlated with total childhood autism symptoms test scores.
“The changes in DNA methylation at differentially methylated CpG sites also correlated with total childhood autism symptoms test scores [ 21 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [21]
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- Authors
- Wong, C. C. Y., Meaburn, E. L., Ronald, A., Price, T. S., Jeffries, A. R., Schalkwyk, L. C., Plomin, R., & Mill, J.
- Affiliations
- King's College London (GB)
- Corresponding author
- Mill, J
- Venue
- Molecular Psychiatry
- Published
- 2013-04-23
- Volume
- 19
- Issue
- 4
- Pages
- 495-503
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3906213
- OpenAlex
- W2148118486
- Cited by
- 327
- References
- 39
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 11 · 2023: 17 · 2022: 23 · 2021: 26 · 2020: 44 · 2019: 28 · 2018: 26 · 2017: 22 · 2016: 24 · 2015: 31 · 2014: 40 · 2013: 15
- FWCI
- 20.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- Research Portal (King's College London) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (publishedVersion, cc-by)
- BIROn (Birkbeck, University of London) (acceptedVersion)
- Open Access at Essex (University of Essex) (acceptedVersion)
- Figshare (submittedVersion)
- Funders
- Autism Speaks
- National Alliance for Research on Schizophrenia and Depression
- King's College Hospital NHS Foundation Trust
- NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
- National Institute for Health and Care Research
- King's College London
- National Institutes of Health (G0901245)
- Medical Research Council (G0901245, G19/2, previously G0500079, G0500079, 295366)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD044454, R01HD046167, HD046167, R01HD044454)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, monozygotic twin discordance, DNA methylation, epigenetics, differentially methylated regions, autistic traits, environmental risk factors
- MeSH terms
- Mental Disorders, Child, Child Development Disorders, Pervasive, Diseases in Twins, Female, United Kingdom, Humans, Male, Phenotype, Psychiatric Status Rating Scales, Twins, Monozygotic, Cohort Studies, CpG Islands, DNA Methylation, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Genome-Wide Association Study, Epigenomics
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