‘— title: “Population-level variation in enhancer expression identifies disease mechanisms in the human brain”

authors:

• Pengfei Dong
• Gabriel E. Hoffman
• Pasha Apontes
• Jaroslav Bendl
• Samir Rahman
• Michael B. Fernando
• Biao Zeng
• James M. Vicari
• Wen Zhang
• Kiran Girdhar
• Kayla G. Townsley
• Ruth Misir
• the CommonMind Consortium
• Kristen J. Brennand
• Vahram Haroutunian
• Georgios Voloudakis
• John F. Fullard
• Panos Roussos

date: “2022-09-26” doi: “10.1038/s41588-022-01170-4”

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publication_types: [“2”]

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publication: “Nature Genetics” publication_short: "”

abstract: Identification of risk variants for neuropsychiatric diseases within enhancers underscores the importance of understanding population-level variation in enhancer function in the human brain. Besides regulating tissue-specific and cell-type-specific transcription of target genes, enhancers themselves can be transcribed. By jointly analyzing large-scale cell-type-specific transcriptome and regulome data, we cataloged 30,795 neuronal and 23,265 non-neuronal candidate transcribed enhancers. Examination of the transcriptome in 1,382 brain samples identified robust expression of transcribed enhancers. We explored gene-enhancer coordination and found that enhancer-linked genes are strongly implicated in neuropsychiatric disease. We identified expression quantitative trait loci (eQTLs) for both genes and enhancers and found that enhancer eQTLs mediate a substantial fraction of neuropsychiatric trait heritability. Inclusion of enhancer eQTLs in transcriptome-wide association studies enhanced functional interpretation of disease loci. Overall, our study characterizes the gene-enhancer regulome and genetic mechanisms in the human cortex in both healthy and diseased states.

Summary. An optional shortened abstract.

summary: Analyses of population-level variation in gene and enhancer expression in the human brain characterize the gene–enhancer regulome and the regulatory mechanisms of transcribed enhancers in neuropsychiatric diseases.

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url_pdf: ‘https://www.nature.com/articles/s41588-022-01170-4' url_code: ‘https://zenodo.org/record/6845955#.Y4OOgdLMJdA' url_dataset: ‘https://doi.org/10.7303/syn25716684' url_poster: '’ url_project: '’ url_slides: '’ url_source: '’ url_video: '’