Histone Acetylome-wide Association Study of Autism Spectrum Disorder

No Thumbnail Available
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.
Journal
Cell
Type
Journal Article
Publisher
Cell Press
Rights
Archived with thanks to Cell
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
Note
This article is freely available via Open Access. Click on the Additional Link above to access the full-text.