Wong C C Y, Meaburn E L, Ronald A, Price T S, Jeffries A R, Schalkwyk L C, Plomin R, Mill J
King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, London, UK.
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.
Mol Psychiatry. 2014 Apr;19(4):495-503. doi: 10.1038/mp.2013.41. Epub 2013 Apr 23.
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.
自闭症谱系障碍（ASD）是一组常见的、复杂的神经发育障碍。尽管ASD的病因有很强的遗传成分，但存在相当多的同卵（MZ）双胞胎不一致情况，这表明非遗传因素也起作用。由于MZ双胞胎共享相同的DNA序列，疾病不一致的MZ双胞胎对为研究环境驱动的表观遗传因素在疾病中的作用提供了理想模型。我们对从一个代表性人群队列中抽取的50对MZ双胞胎（100人）样本进行了全基因组DNA甲基化分析，该队列包括在ASD、ASD相关特征和无自闭症表型方面不一致和一致的双胞胎。双胞胎内部和组间分析确定了许多与ASD相关的差异甲基化区域。此外，我们报告了在整个样本队列中DNA甲基化与定量测量的自闭症特征分数之间存在显著相关性。这项研究代表了对ASD不一致的MZ双胞胎进行的首次系统表观基因组分析，并暗示DNA甲基化改变在自闭症中起作用。
