| Literature DB >> 36163279 |
Pengfei Dong1,2,3,4,5, Gabriel E Hoffman1,3,4,5, Pasha Apontes2,3,4,5,6, Jaroslav Bendl1,2,3,4,5, Samir Rahman1,2,3,4,5, Michael B Fernando2,7,8, Biao Zeng1,2,3,4,5, James M Vicari1,2,3,4,5, Wen Zhang2,3,4,5, Kiran Girdhar1,2,3,4,5, Kayla G Townsley2,7, Ruth Misir2,3,4,5, Kristen J Brennand2,4,7,8,9, Vahram Haroutunian2,4,6,7, Georgios Voloudakis1,2,4, John F Fullard1,2,3,4,5, Panos Roussos10,11,12,13,14,15,16.
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.Entities:
Mesh：
Year: 2022 PMID： 36163279 PMCID： PMC9547946 DOI： 10.1038/s41588-022-01170-4
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307