Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity.
Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity.
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DOI：
10.3390/genes12091433
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发表时间：
2021-09-17
期刊：
影响因子：
3.5
通讯作者：
Brentani H
中科院分区：
文献类型：
--
作者：
Neri de Souza Reis V;Tahira AC;Daguano Gastaldi V;Mari P;Portolese J;Feio Dos Santos AC;Lisboa B;Mari J;Caetano SC;Brunoni D;Bordini D;Silvestre de Paula C;Vêncio RZN;Quackenbush J;Brentani H
虽然自闭症谱系障碍（ASD）被认为是严重影响遗传因素，表观遗传和环境因素的作用仍在建立。本研究旨在根据家族史和宫内环境应激暴露来确定ASD脆弱性成分，探索可能的脆弱性亚组，访问DNA甲基化年龄加速（AA）作为生活中应激暴露的代理，并评估ASD脆弱性成分和AA与表型严重程度措施的关联。采用主成分分析法（PCA）对67名孤独症儿童母亲的脆弱性进行分析。我们发现，PC1与心理社会压力（母亲压力，母亲教育和社会阶层）有较高的相关性，PC2与生物因素（精神病家族史和妊娠并发症）有较高的相关性。比较高于和低于PC1平均值亚组之间的甲基化组，我们发现11，879个统计学显著差异甲基化探针（DMP，p < 0.05）。DMPs的CpG位点富集在VMR中，大多数表现出环境和遗传的影响。超甲基化探针在与功能性SNP相关的不同调控区中呈现较高的比率，表明亚组可能具有不同的受影响调控区，并且其对疾病的易感性由共同变异解释。由表观遗传时钟AA调节的脆弱性成分评分与Vineland总分相关（p = 0.0036，adjR2 = 0.31），表明具有压力负担的风险因素可以影响ASD表型。
Although Autism Spectrum Disorders (ASD) is recognized as being heavily influenced by genetic factors, the role of epigenetic and environmental factors is still being established. This study aimed to identify ASD vulnerability components based on familial history and intrauterine environmental stress exposure, explore possible vulnerability subgroups, access DNA methylation age acceleration (AA) as a proxy of stress exposure during life, and evaluate the association of ASD vulnerability components and AA to phenotypic severity measures. Principal Component Analysis (PCA) was used to search the vulnerability components from 67 mothers of autistic children. We found that PC1 had a higher correlation with psychosocial stress (maternal stress, maternal education, and social class), and PC2 had a higher correlation with biological factors (psychiatric family history and gestational complications). Comparing the methylome between above and below PC1 average subgroups we found 11,879 statistically significant differentially methylated probes (DMPs, p < 0.05). DMPs CpG sites were enriched in variably methylated regions (VMRs), most showing environmental and genetic influences. Hypermethylated probes presented higher rates in different regulatory regions associated with functional SNPs, indicating that the subgroups may have different affected regulatory regions and their liability to disease explained by common variations. Vulnerability components score moderated by epigenetic clock AA was associated with Vineland Total score (p = 0.0036, adjR2 = 0.31), suggesting risk factors with stress burden can influence ASD phenotype.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
3.7
作者：
Delobel-Ayoub M;Ehlinger V;Klapouszczak D;Maffre T;Raynaud JP;Delpierre C;Arnaud C
通讯作者：
Arnaud C
影响因子：
16.6
作者：
Andrews SV;Ellis SE;Bakulski KM;Sheppard B;Croen LA;Hertz-Picciotto I;Newschaffer CJ;Feinberg AP;Arking DE;Ladd-Acosta C;Fallin MD
通讯作者：
Fallin MD
DOI：
10.1038/nrn.2016.41
发表时间：
2016-07
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Vogel Ciernia A;LaSalle J
通讯作者：
LaSalle J
影响因子：
3.9
作者：
Fernell E;Eriksson MA;Gillberg C
通讯作者：
Gillberg C