TY - JOUR
T1 - Histone Acetylome-wide Association Study of Autism Spectrum Disorder
AU - Sun, Wenjie
AU - Poschmann, Jeremie
AU - Cruz-Herrera del Rosario, Ricardo
AU - Parikshak, Neelroop N.
AU - Hajan, Hajira Shreen
AU - Kumar, Vibhor
AU - Ramasamy, Ramalakshmi
AU - Belgard, T. Grant
AU - Elanggovan, Bavani
AU - Wong, Chloe Chung Yi
AU - Mill, Jonathan
AU - Geschwind, Daniel H.
AU - Prabhakar, Shyam
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/11/17
Y1 - 2016/11/17
N2 - 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.
AB - 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.
KW - autism spectrum disorder
KW - disease-epigenetic alterations
KW - epigenetics
KW - histone acetylation
KW - histone acetylation quantitative trait loci
KW - regulome profiling
UR - https://www.scopus.com/pages/publications/84995757367
U2 - 10.1016/j.cell.2016.10.031
DO - 10.1016/j.cell.2016.10.031
M3 - Article
C2 - 27863250
AN - SCOPUS:84995757367
SN - 0092-8674
VL - 167
SP - 1385-1397.e11
JO - Cell
JF - Cell
IS - 5
ER -