ArticleMolecular brain2019
Genetic risk variants for brain disorders are enriched in cortical H3K27ac domains.
Article in Molecular brain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Pooled it
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- Transcriptomic and epigenomic consequences of heterozygous loss-of-function mutations in AKAP11, a shared risk gene for bipolar disorder and schizophrenia.Molecular psychiatry · 2025Article
- The APOE isoforms differentially shape the transcriptomic and epigenomic landscapes of human microglia xenografted into a mouse model of Alzheimer's disease.Nature communications · 2025Article
- CHAS infers cell type-specific signatures in bulk brain histone acetylation studies of neurological and psychiatric disorders.Cell reports methods · 2025Article
- CUT&Tag recovers up to half of ENCODE ChIP-seq histone acetylation peaks.Nature communications · 2025Article
- A statistical framework to identify cell types whose genetically regulated proportions are associated with complex diseases.PLoS genetics · 2023Article
- EpiCompare: R package for the comparison and quality control of epigenomic peak files.Bioinformatics advances · 2023Article
- Methylation of the tyrosine hydroxylase gene is dysregulated by cocaine dependence in the human striatum.iScience · 2021Article
- Chromatin Alterations in Neurological Disorders and Strategies of (Epi)Genome Rescue.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Cocaine-related DNA methylation in caudate neurons alters 3D chromatin structure of the IRXA gene cluster.Molecular psychiatry · 2021Article
- Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism.Nature communications · 2020Article
- Genomic mechanisms in Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2020Review
- A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders.Nature communications · 2020Article
- Omics in Neurodegenerative Disease: Hope or Hype?Trends in genetics : TIG · 2020Review
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
Most variants associated with complex phenotypes in genome-wide association studies (GWAS) do not directly index coding changes affecting protein structure. Instead they are hypothesized to influence gene regulation, with common variants associated with disease being enriched in regulatory domains including enhancers and regions of open chromatin. There is interest, therefore, in using epigenomic annotation data to identify the specific regulatory mechanisms involved and prioritize risk variants. We quantified lysine H3K27 acetylation (H3K27ac) - a robust mark of active enhancers and promoters that is strongly correlated with gene expression and transcription factor binding - across the genome in entorhinal cortex samples using chromatin immunoprecipitation followed by highly parallel sequencing (ChIP-seq). H3K27ac peaks were called using high quality reads combined across all samples and formed the basis of partitioned heritability analysis using LD score regression along with publicly-available GWAS results for seven psychiatric and neurodegenerative traits. Heritability for all seven brain traits was significantly enriched in these H3K27ac peaks (enrichment ranging from 1.09-2.13) compared to regions of the genome containing other active regulatory and functional elements across multiple cell types and tissues. The strongest enrichments were for amyotrophic lateral sclerosis (ALS) (enrichment = 2.19; 95% CI = 2.12-2.27), autism (enrichment = 2.11; 95% CI = 2.05-2.16) and major depressive disorder (enrichment = 2.04; 95% CI = 1.92-2.16). Much lower enrichments were observed for 14 non-brain disorders, although we identified enrichment in cortical H3K27ac domains for body mass index (enrichment = 1.16; 95% CI = 1.13-1.19), ever smoked (enrichment = 2.07; 95% CI = 2.04-2.10), HDL (enrichment = 1.53; 95% CI = 1.45-1.62) and trigylcerides (enrichment = 1.33; 95% CI = 1.24-1.42). These results indicate that risk alleles for brain disorders are preferentially located in regions of regulatory/enhancer function in the cortex, further supporting the hypothesis that genetic variants for these phenotypes influence gene regulation in the brain.
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