小柯机器人

美国西奈山伊坎医学院Panos Roussos小组发现，增强子表达的群体水平变异鉴定出人类大脑的疾病机制。相关论文于2022年9月26日在线发表在《自然—遗传学》杂志上。

Title: Population-level variation in enhancer expression identifies disease mechanisms in the human brain

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

Issue&Volume: 2022-09-26

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.

DOI: 10.1038/s41588-022-01170-4

Source: https://www.nature.com/articles/s41588-022-01170-4

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex