Histone Acetylome-wide Association Study of Autism Spectrum Disorder

2.50
Hdl Handle:
http://hdl.handle.net/11287/620270
Title:
Histone Acetylome-wide Association Study of Autism Spectrum Disorder
Authors:
Sun, W.; Poschmann, J.; Cruz-Herrera del Rosario, R.; Parikshak, N. N.; Hajan, H. S.; Kumar, V.; Ramasamy, R.; Belgard, T. G.; Elanggovan, B.; Wong, C. C. Y.; Mill, Jonathan; Geschwind, D. H.; Prabhakar, S.
Abstract:
The association of histone modification changes with autism spectrum disorder (ASD) has not been systematically examined. We conducted a histone acetylome-wide association study (HAWAS) by performing H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) on 257 postmortem samples from ASD and matched control brains. Despite etiological heterogeneity, ≥68% of syndromic and idiopathic ASD cases shared a common acetylome signature at >5,000 cis-regulatory elements in prefrontal and temporal cortex. Similarly, multiple genes associated with rare genetic mutations in ASD showed common “epimutations.” Acetylome aberrations in ASD were not attributable to genetic differentiation at cis-SNPs and highlighted genes involved in synaptic transmission, ion transport, epilepsy, behavioral abnormality, chemokinesis, histone deacetylation, and immunity. By correlating histone acetylation with genotype, we discovered >2,000 histone acetylation quantitative trait loci (haQTLs) in human brain regions, including four candidate causal variants for psychiatric diseases. Due to the relative stability of histone modifications postmortem, we anticipate that the HAWAS approach will be applicable to multiple diseases.
Citation:
Histone Acetylome-wide Association Study of Autism Spectrum Disorder 2016, 167 (5):1385 Cell
Publisher:
Cell Press
Journal:
Cell
Issue Date:
Nov-2016
URI:
http://hdl.handle.net/11287/620270
DOI:
10.1016/j.cell.2016.10.031
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0092867416314519
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text.
Type:
Journal Article
Language:
en
ISSN:
00928674
Appears in Collections:
Honorary contracts publications; 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorSun, W.en
dc.contributor.authorPoschmann, J.en
dc.contributor.authorCruz-Herrera del Rosario, R.en
dc.contributor.authorParikshak, N. N.en
dc.contributor.authorHajan, H. S.en
dc.contributor.authorKumar, V.en
dc.contributor.authorRamasamy, R.en
dc.contributor.authorBelgard, T. G.en
dc.contributor.authorElanggovan, B.en
dc.contributor.authorWong, C. C. Y.en
dc.contributor.authorMill, Jonathanen
dc.contributor.authorGeschwind, D. H.en
dc.contributor.authorPrabhakar, S.en
dc.date.accessioned2017-03-13T10:06:33Z-
dc.date.available2017-03-13T10:06:33Z-
dc.date.issued2016-11-
dc.identifier.citationHistone Acetylome-wide Association Study of Autism Spectrum Disorder 2016, 167 (5):1385 Cellen
dc.identifier.issn00928674-
dc.identifier.doi10.1016/j.cell.2016.10.031-
dc.identifier.urihttp://hdl.handle.net/11287/620270-
dc.description.abstractThe association of histone modification changes with autism spectrum disorder (ASD) has not been systematically examined. We conducted a histone acetylome-wide association study (HAWAS) by performing H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) on 257 postmortem samples from ASD and matched control brains. Despite etiological heterogeneity, ≥68% of syndromic and idiopathic ASD cases shared a common acetylome signature at >5,000 cis-regulatory elements in prefrontal and temporal cortex. Similarly, multiple genes associated with rare genetic mutations in ASD showed common “epimutations.” Acetylome aberrations in ASD were not attributable to genetic differentiation at cis-SNPs and highlighted genes involved in synaptic transmission, ion transport, epilepsy, behavioral abnormality, chemokinesis, histone deacetylation, and immunity. By correlating histone acetylation with genotype, we discovered >2,000 histone acetylation quantitative trait loci (haQTLs) in human brain regions, including four candidate causal variants for psychiatric diseases. Due to the relative stability of histone modifications postmortem, we anticipate that the HAWAS approach will be applicable to multiple diseases.en
dc.language.isoenen
dc.publisherCell Pressen
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0092867416314519en
dc.rightsArchived with thanks to Cellen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleHistone Acetylome-wide Association Study of Autism Spectrum Disorderen
dc.typeJournal Articleen
dc.identifier.journalCellen
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text.en
dc.type.versionPublisheden
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