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.
journal_name
Celljournal_title
Cellauthors
Sun W,Poschmann J,Cruz-Herrera Del Rosario R,Parikshak NN,Hajan HS,Kumar V,Ramasamy R,Belgard TG,Elanggovan B,Wong CCY,Mill J,Geschwind DH,Prabhakar Sdoi
10.1016/j.cell.2016.10.031subject
Has Abstractpub_date
2016-11-17 00:00:00pages
1385-1397.e11issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(16)31451-9journal_volume
167pub_type
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