title: Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits.
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.
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, London, UK.
authors.forename: C C Y
authors.initials: CC
authors.lastname: Wong
authors.affiliation: 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.
authors.forename: E L
authors.initials: EL
authors.lastname: Meaburn
authors.affiliation: 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.
authors.forename: A
authors.initials: A
authors.lastname: Ronald
authors.affiliation: 1] King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, London, UK [2] Institute of Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, PA, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: Price
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, London, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Jeffries
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, London, UK.
authors.forename: L C
authors.initials: LC
authors.lastname: Schalkwyk
authors.affiliation: King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Plomin
authors.affiliation: 1] King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, London, UK [2] University of Exeter Medical School, Exeter University, St Luke's Campus, Exeter, UK.
authors.forename: J
authors.initials: J
authors.lastname: Mill
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000150:complications* / Q000235:genetics*; D015331:Cohort Studies; D018899:CpG Islands; D019175:DNA Methylation; D004200:Diseases in Twins / Q000235:genetics*; D057890:Epigenomics; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000209:etiology* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D014430:Twins, Monozygotic / Q000235:genetics; D006113:United Kingdom