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

Gokul Ramaswami, Hyejung Won, Michael J. Gandal, Jillian Haney, Jerry C. Wang, Chloe C. Y. Wong, Wenjie Sun, Shyam Prabhakar, Jonathan Mill and Daniel H. Geschwind ()
Additional contact information
Gokul Ramaswami: University of California Los Angeles
Hyejung Won: University of California Los Angeles
Michael J. Gandal: University of California Los Angeles
Jillian Haney: University of California Los Angeles
Jerry C. Wang: University of California Los Angeles
Chloe C. Y. Wong: Institute of Psychiatry, Psychology and Neuroscience, King’s College London
Wenjie Sun: Computational and Systems Biology, Genome Institute of Singapore
Shyam Prabhakar: Computational and Systems Biology, Genome Institute of Singapore
Jonathan Mill: University of Exeter
Daniel H. Geschwind: University of California Los Angeles

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18526-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18526-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18526-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().