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

被引：199

作者：

Wong, C. C. Y. ^{[1
]}

Meaburn, E. L. ^{[1
,2
]}

Ronald, A. ^{[1
,2
]}

Price, T. S. ^{[1
,3
]}

Jeffries, A. R. ^{[1
]}

Schalkwyk, L. C. ^{[1
]}

Plomin, R. ^{[1
]}

Mill, J. ^{[1
,4
]}

机构：

[1] Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, Inst Psychiat, London SE5 8AF, England

[2] Univ London, Dept Psychol Sci, London, England

[3] Univ Penn, Inst Translat Med & Therapeut, Sch Med, Philadelphia, PA 19104 USA

[4] Univ Exeter, Sch Med, Exeter, Devon, England

来源：

MOLECULAR PSYCHIATRY | 2014年 / 19卷 / 04期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

ASD; autism; copy-number variation; DNA methylation; epigenetics; monozygotic twins; HIDDEN-MARKOV MODEL; SNP GENOTYPING DATA; DNA METHYLATION; BIPOLAR DISORDER; EPIGENETICS; GENOME; BRAIN; SPECIFICITY; POPULATION; CHILDHOOD;

D O I：

10.1038/mp.2013.41

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：495 / 503

页数：9

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