RT Journal Article
SR Electronic
T1 Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 718932
DO 10.1101/718932
A1 Gokul Ramaswami
A1 Hyejung Won
A1 Michael J. Gandal
A1 Jillian Haney
A1 Jerry C. Wang
A1 Chloe C.Y. Wong
A1 Wenjie Sun
A1 Shyam Prabhakar
A1 Jonathan Mill
A1 Daniel H. Geschwind
YR 2020
UL http://biorxiv.org/content/early/2020/01/23/718932.abstract
AB 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.