Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits
Mol Psychiatry. 2014 Apr;19(4):495-503. doi: 10.1038/mp.2013.41. Epub 2013 Apr 23.
Wong CC1, Meaburn EL2, Ronald A2, Price TS3, Jeffries AR1, Schalkwyk LC1, Plomin R1, Mill J4.
1King’s College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, London, UK;
2Department of PsychologicalSciences, Birkbeck, University of London, London, UK;
3Institute of Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, PA, USA and
4University of Exeter Medical School, Exeter University, St Luke’s Campus, Exeter, UK. Correspondence: Dr J Mill, MRC Social, Genetic and Developmental Psychiatry Centre,
Institute of Psychiatry, King’s College London, Denmark Hill, De Crespigny Park, London SE5 8AF, UK
Abstract
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.
Exerpt
“These findings concur with mounting data suggesting that environmentally mediated effects on the epigenome may be relatively common and important for disease.”
