Histone Acetylome-wide Association Study of Autism Spectrum Disorder | Zendy

Wenjie Sun | Zendy; Jérémie Poschmann | Zendy; Ricardo Cruz-Herrera del Rosario | Zendy; Neelroop Parikshak | Zendy; Hajira Shreen Hajan | Zendy; Vibhor Kumar | Zendy; Ramalakshmi Ramasamy | Zendy; T. Grant Belgard | Zendy; Bavani Elanggovan | Zendy; Chloe C. Y. Wong | Zendy; Jonathan Mill | Zendy; Daniel H. Geschwind | Zendy; Shyam Prabhakar | Zendy

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Histone Acetylome-wide Association Study of Autism Spectrum Disorder

Author(s) -

Wenjie Sun,

Jérémie Poschmann,

Ricardo Cruz-Herrera del Rosario,

Neelroop Parikshak,

Hajira Shreen Hajan,

Vibhor Kumar,

Ramalakshmi Ramasamy,

T. Grant Belgard,

Bavani Elanggovan,

Chloe C. Y. Wong,

Jonathan Mill,

Daniel H. Geschwind,

Shyam Prabhakar

Publication year - 2016

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2016.10.031

Subject(s) - biology , autism spectrum disorder , histone , association (psychology) , autism , genetics , computational biology , microbiology and biotechnology , gene , developmental psychology , psychology , philosophy , epistemology

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.

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