Genome-Wide DNA Methylation Analysis Reveals Epigenetic Pattern of SH2B1 in Chinese Monozygotic Twins Discordant for Autism Spectrum Disorder

Liang, Shuang; Li, Zhenzhi; Wang, Yihan; Li, Xiaodan; Yang, Xiaolei; Zhan, Xiaolei; Huang, Yan; Gao, Zhaomin; Zhang, Min; Sun, Chongde; Zhang, Yan; Wu, Lijie

doi:10.3389/fnins.2019.00712

Cited by 27 publications

(18 citation statements)

References 47 publications

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“…The study by Wong et al (2014) described methylation differences within each pair of discordant twins that were generally family specific as well as group differences between the combined cases and controls. The latter study by Liang et al (2019) reported more than 2300 DAGs between discordant Chinese MZ twins that were associated with a number of KEGG pathways, including the mTOR, axon guidance, and neurotrophin signaling pathways identified in our study. Interestingly, 10 of the 35 neurotrophin signaling genes identified by Liang et al (2019) are also represented in this study.…”

Section: Discussionmentioning

confidence: 57%

“…It should be noted that the use of discordant MZ twins is particularly advantageous for methylation studies in that the identical genotype allows for better resolution of epigenetic factors associated with a complex disorder. Since the study by Nguyen et al (2010), two other studies employing discordant MZ twins have reported genome-wide differences in DNA methylation associated with ASD (Liang et al, 2019; Wong et al, 2014). The study by Wong et al (2014) described methylation differences within each pair of discordant twins that were generally family specific as well as group differences between the combined cases and controls.…”

Section: Discussionmentioning

confidence: 99%

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Altered DNA methylation in a severe subtype of idiopathic autism: Evidence for sex differences in affected metabolic pathways

Yang

et al. 2020

Autism

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Although differences in DNA methylation have been associated with both syndromic and idiopathic autism, differential methylation has not been examined previously with respect to sex differences. The goals of this study were to (1) identify differences in the DNA methylation profiles of lymphoblastoid cell lines derived from a subgroup of severely affected individuals with idiopathic autism and their respective sex-matched siblings, (2) describe autism spectrum disorder–relevant pathways and functions that may be impacted by differentially methylated genes, and (3) investigate sex-dependent differences in methylation patterns and signaling pathways. Our results revealed significant differences in DNA methylation in cells from individuals with idiopathic autism spectrum disorders and from their unaffected sex-matched siblings. The samples were divided either by sex or by separation into discovery and validation groups. The genes in differentially methylated regions were statistically enriched in autism susceptibility genes and canonical pathways commonly associated with autism spectrum disorders, including synaptogenesis, semaphorin, and mammalian target of rapamycin signaling pathways. Differentially methylated region–associated genes in females were additionally associated with pathways that implicate mitochondrial dysfunction and metabolic disorders that may offer some protection against autism spectrum disorders. Further investigations of sex differences are required to develop a fuller understanding of the pathobiology, gene regulatory mechanisms, and differential susceptibility of males and females toward autism spectrum disorders. Lay abstract This study investigates altered DNA methylation that may contribute to autism spectrum disorders. DNA methylation is an epigenetic mechanism for regulating the level at which genes are expressed, and is thus complementary to genetics and gene expression analyses which look at the variations in gene structure and gene products in cells. Here, we identify DNA methylation differences between autistic and sex-matched non-autistic siblings, focusing on a subgroup of severely affected individuals with language impairment to reduce the clinical heterogeneity among the cases. Our results show significant differentially methylated genes between the sibling groups that are enriched in autism risk genes as well as in signaling and biochemical pathways previously associated with the pathobiology of autism spectrum disorders. Moreover, we show for the first time that these differences are in part sex dependent, with differentially methylated genes in females associated with pathways that implicate mitochondrial dysfunction and metabolic disorders that may offer some protection to females against autism spectrum disorders. Further investigations of sex differences are required to develop a fuller understanding of the pathobiology, gene regulatory mechanisms, and differential susceptibility of males and females toward autism spectrum disorders.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Altered DNA methylation in a severe subtype of idiopathic autism: Evidence for sex differences in affected metabolic pathways

Yang

et al. 2020

Autism

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“…Liang et al. [ 108 ], analyzed 5 ASD-discordant monozygotic twins and found 2,397 differentially methylated genes. Among these genes, the methylation of SH2B1 gene was further studied.…”

Section: Epigenetics Of Autism Spectrum Disordermentioning

confidence: 99%

Gut microbiota metabolites in autistic children: An epigenetic perspective

Sabit

Tombuloğlu

Rehman

et al. 2021

Heliyon

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Gut microbiota has become an issue of great importance recently due to its major role in autism spectrum disorder (ASD). Over the past three decades, there has been a sustained research activity focused to explain the actual mechanism by which gut microbiota triggers/develops autism. Several genetic and epigenetic factors are involved in this disorder, with epigenetics being the most active area of research. Although the constant investigation and advancements, epigenetic implications in ASD still need a deeper functional/causal analysis. In this review, we describe the major gut microbiota metabolites and how they induce epigenetic changes in ASD along with interactions through the gut-brain axis.

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“…Later, many researchers started using “bisulfite” to differentiate cytosine and methylated cytosine in studies that examine DNA methylation (Kinoshita et al 2013 ; Liang et al 2019 ). With bisulfite, cytosine is deaminated and converted to uracil, while methylated cytosine is left in its original state.…”

Section: Mz Studies Of Molecular Geneticsmentioning

confidence: 99%

“…The similarity of the genetic information in MZs provides a useful means for determining the disorder-causing role of environmental factors. In recent years, studies on the differences between genomic and epigenomic characteristics of MZs have led to the development of new approaches for elucidating the etiology of psychiatric disorders (Liang et al 2019 ; Morimoto et al 2017 ). The current paper focuses on epidemiological and molecular genetic research studies in MZs with the purpose of unravelling useful insights on factors that can lead to SCZ and ASD.…”

Section: Introductionmentioning

confidence: 99%

Genetic and environmental factors of schizophrenia and autism spectrum disorder: insights from twin studies

et al. 2020

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Twin studies of psychiatric disorders such as schizophrenia and autism spectrum disorder have employed epidemiological approaches that determine heritability by comparing the concordance rate between monozygotic twins (MZs) and dizygotic twins. The basis for these studies is that MZs share 100% of their genetic information. Recently, biological studies based on molecular methods are now being increasingly applied to examine the differences between MZs discordance for psychiatric disorders to unravel their possible causes. Although recent advances in next-generation sequencing have increased the accuracy of this line of research, there has been greater emphasis placed on epigenetic changes versus DNA sequence changes as the probable cause of discordant psychiatric disorders in MZs. Since the epigenetic status differs in each tissue type, in addition to the DNA from the peripheral blood, studies using DNA from nerve cells induced from postmortem brains or induced pluripotent stem cells are being carried out. Although it was originally thought that epigenetic changes occurred as a result of environmental factors, and thus were not transmittable, it is now known that such changes might possibly be transmitted between generations. Therefore, the potential possible effects of intestinal flora inside the body are currently being investigated as a cause of discordance in MZs. As a result, twin studies of psychiatric disorders are greatly contributing to the elucidation of genetic and environmental factors in the etiology of psychiatric conditions.

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Genome-Wide DNA Methylation Analysis Reveals Epigenetic Pattern of SH2B1 in Chinese Monozygotic Twins Discordant for Autism Spectrum Disorder

Cited by 27 publications

References 47 publications

Altered DNA methylation in a severe subtype of idiopathic autism: Evidence for sex differences in affected metabolic pathways

Altered DNA methylation in a severe subtype of idiopathic autism: Evidence for sex differences in affected metabolic pathways

Gut microbiota metabolites in autistic children: An epigenetic perspective

Genetic and environmental factors of schizophrenia and autism spectrum disorder: insights from twin studies

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