Methylomic Analysis of Monozygotic Twins Discordant for Autism Spectrum Disorder and Related Behavioural Traits

C.C.Y. Wong1, E.L. Meaburn1,2, A. Ronald1,2, T.S. Price1,3, A.R. Jeffries1, L.C. Schalkwyk1, R.Plomin1, J. Mill1,4

  1. King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, London, UK
  2. Department of Psychological Sciences, Birkbeck, University of London, London, UK
  3. Institute of Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, PA, USA
  4. University of Exeter Medical School, Exeter University, St Luke's Campus, Exeter, UK


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.

Link to manuscript

ASD twin data

  1. ASD Discordant MZ Twins_Within Twin Correlation.pdf - correlation plots for each of our ASD-discordant MZ twin pair.
  2. ASDtwins_27KData.csv - listing transformed beta values for each CpG included in our analysis