Histone Acetylome-wide Association Study of Autism Spectrum Disorder

Wenjie Sun; Jeremie Poschmann; Ricardo Cruz-Herrera del Rosario; Neelroop N. Parikshak; Hajira Shreen Hajan; Vibhor Kumar; Ramalakshmi Ramasamy; T. Grant Belgard; Bavani Elanggovan; Chloe Chung Yi Wong; Jonathan Mill; Daniel H. Geschwind; Shyam Prabhakar

doi:10.1016/j.cell.2016.10.031

Histone Acetylome-wide Association Study of Autism Spectrum Disorder

Wenjie Sun, Jeremie Poschmann, Ricardo Cruz-Herrera del Rosario, Neelroop N. Parikshak, Hajira Shreen Hajan, Vibhor Kumar, Ramalakshmi Ramasamy, T. Grant Belgard, Bavani Elanggovan, Chloe Chung Yi Wong, Jonathan Mill, Daniel H. Geschwind^*, Shyam Prabhakar

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	1385-1397.e11
Number of pages	1
Journal	Cell
Volume	167
Issue number	5
Early online date	17 Nov 2016
DOIs	https://doi.org/10.1016/j.cell.2016.10.031
Publication status	Published - 17 Nov 2016

Keywords

autism spectrum disorder
disease-epigenetic alterations
epigenetics
histone acetylation
histone acetylation quantitative trait loci
regulome profiling

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Histone Acetylome-wide_SUN_Accepted18October2016_GOLD VoRFinal published version, 2.5 MBLicence: CC BY-NC-ND

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title = "Histone Acetylome-wide Association Study of Autism Spectrum Disorder",

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.",

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AU - Hajan, Hajira Shreen

AU - Kumar, Vibhor

AU - Ramasamy, Ramalakshmi

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AU - Wong, Chloe Chung Yi

AU - Mill, Jonathan

AU - Geschwind, Daniel H.

AU - Prabhakar, Shyam

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Histone Acetylome-wide Association Study of Autism Spectrum Disorder

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