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Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism.

ABSTRACT: Autism spectrum disorder (ASD) is a phenotypically and genetically heterogeneous neurodevelopmental disorder. Despite this heterogeneity, previous studies have shown patterns of molecular convergence in post-mortem brain tissue from autistic subjects. Here, we integrate genome-wide measures of mRNA expression, miRNA expression, DNA methylation, and histone acetylation from ASD and control brains to identify a convergent molecular subtype of ASD with shared dysregulation across both the epigenome and transcriptome. Focusing on this convergent subtype, we substantially expand the repertoire of differentially expressed genes in ASD and identify a component of upregulated immune processes that are associated with hypomethylation. We utilize eQTL and chromosome conformation datasets to link differentially acetylated regions with their cognate genes and identify an enrichment of ASD genetic risk variants in hyperacetylated noncoding regulatory regions linked to neuronal genes. These findings help elucidate how diverse genetic risk factors converge onto specific molecular processes in ASD.

SUBMITTER: Ramaswami G

PROVIDER: S-EPMC7519165 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism.

Ramaswami Gokul G Won Hyejung H Gandal Michael J MJ Haney Jillian J Wang Jerry C JC Wong Chloe C Y CCY Sun Wenjie W Prabhakar Shyam S Mill Jonathan J Geschwind Daniel H DH

Nature communications 20200925 1

Autism spectrum disorder (ASD) is a phenotypically and genetically heterogeneous neurodevelopmental disorder. Despite this heterogeneity, previous studies have shown patterns of molecular convergence in post-mortem brain tissue from autistic subjects. Here, we integrate genome-wide measures of mRNA expression, miRNA expression, DNA methylation, and histone acetylation from ASD and control brains to identify a convergent molecular subtype of ASD with shared dysregulation across both the epigenome ...[more]

PMID: 32978376

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Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism.

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Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism.

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