Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits

TY - JOUR

T1 - Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits

AU - Wong, Chloe

AU - Meaburn, E L

AU - Ronald, A

AU - Price, T S

AU - Jeffries, A R

AU - Schalkwyk, L C

AU - Plomin, R

AU - Mill, J

PY - 2014/4/23

Y1 - 2014/4/23

N2 - 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.

AB - 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.

KW - ASD

KW - Autism

KW - Copy-number variation

KW - DNA methylation

KW - Epigenetics

KW - Monozygotic twins

U2 - 10.1038/mp.2013.41

DO - 10.1038/mp.2013.41

M3 - Article

C2 - 23608919

VL - 19

SP - 495

EP - 503

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 4

ER -