Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder.
Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder.
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DOI：
10.1038/s41467-017-00868-y
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发表时间：
2017-10-24
影响因子：
16.6
通讯作者：
Fallin MD
中科院分区：
文献类型：
--
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
整合新兴的表观遗传信息与自闭症谱系障碍（ASD）的遗传结果可能阐明功能的见解不可能通过任何类型的信息孤立。在这里，我们使用来自脐带血和外周血的基因型和DNA甲基化（DNAm）数据来鉴定与DNA甲基化相关的SNP（meQTL列表）。此外，我们使用公开可用的胎儿脑和肺meQTL列表来评估ASD GWAS结果对组织特异性meQTL的富集。ASD相关SNP在胎儿脑（OR = 3.55; P < 0.001）和外周血meQTL（OR = 1.58; P < 0.001）中富集。跨越脐带、血液和脑组织的ASD meQTL的CpG靶标富集免疫相关途径，与ASD中的其他表达和DNAm结果一致，并揭示了不受遗传发现影响的途径。基因型和DNAm的联合分析表明，大脑和血液中的DNAm都有可能更广泛地洞察ASD和精神病表型。“最近有一些关于自闭症谱系障碍的表观遗传学研究。在这里，作者整合了来自脐带血和外周血以及脑组织的遗传和表观遗传数据，以显示基于血液的表观遗传数据在深入了解精神疾病方面的潜力。
Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly. “There have been a number of recent epigenetic studies on autism spectrum disorder. Here, the authors integrate genetic and epigenetic data from cord and peripheral blood and also from brain tissues to show the potential of blood-based epigenetic data to provide insights into psychiatric disorders.”
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影响因子：
6.2
作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
通讯作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
影响因子：
25
作者：
Hannon E;Spiers H;Viana J;Pidsley R;Burrage J;Murphy TM;Troakes C;Turecki G;O'Donovan MC;Schalkwyk LC;Bray NJ;Mill J
通讯作者：
Mill J
影响因子：
3.7
作者：
Hannon E;Lunnon K;Schalkwyk L;Mill J
通讯作者：
Mill J
影响因子：
7.7
作者：
Feinberg, Jason I.;Bakulski, Kelly M.;Feinberg, Andrew P.
通讯作者：
Feinberg, Andrew P.