Histone Acetylome-wide Association Study of Autism Spectrum Disorder.
Cell
; 167(5): 1385-1397.e11, 2016 11 17.
Article
en En
| MEDLINE
| ID: mdl-27863250
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Lóbulo Temporal
/
Cerebelo
/
Corteza Prefrontal
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Sitios de Carácter Cuantitativo
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Código de Histonas
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Trastorno del Espectro Autista
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2016
Tipo del documento:
Article
País de afiliación:
Singapur