人群规模组织转录组学将长非编码 RNA 映射到复杂疾病。
Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease.
机构信息
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
出版信息
Cell. 2021 May 13;184(10):2633-2648.e19. doi: 10.1016/j.cell.2021.03.050. Epub 2021 Apr 16.
Abstract
Long non-coding RNA (lncRNA) genes have well-established and important impacts on molecular and cellular functions. However, among the thousands of lncRNA genes, it is still a major challenge to identify the subset with disease or trait relevance. To systematically characterize these lncRNA genes, we used Genotype Tissue Expression (GTEx) project v8 genetic and multi-tissue transcriptomic data to profile the expression, genetic regulation, cellular contexts, and trait associations of 14,100 lncRNA genes across 49 tissues for 101 distinct complex genetic traits. Using these approaches, we identified 1,432 lncRNA gene-trait associations, 800 of which were not explained by stronger effects of neighboring protein-coding genes. This included associations between lncRNA quantitative trait loci and inflammatory bowel disease, type 1 and type 2 diabetes, and coronary artery disease, as well as rare variant associations to body mass index.
摘要
长非编码 RNA（lncRNA）基因对分子和细胞功能具有既定且重要的影响。然而，在数千个 lncRNA 基因中，确定与疾病或特征相关的亚组仍然是一个主要挑战。为了系统地描述这些 lncRNA 基因，我们使用基因型组织表达（GTEx）项目 v8 遗传和多组织转录组数据，对 49 种组织中 14100 个 lncRNA 基因的表达、遗传调控、细胞环境和 101 种不同复杂遗传特征的相关性进行了分析。通过这些方法，我们确定了 1432 个 lncRNA 基因-特征相关性，其中 800 个与邻近蛋白质编码基因的更强效应无关。这包括 lncRNA 数量性状基因座与炎症性肠病、1 型和 2 型糖尿病以及冠状动脉疾病之间的相关性，以及与体重指数相关的罕见变异相关性。
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1
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Nat Genet. 2021 Sep;53(9):1290-1299. doi: 10.1038/s41588-021-00924-w. Epub 2021 Sep 6.
2
Non-coding deletions identify Maenli lncRNA as a limb-specific En1 regulator.非编码缺失鉴定 Maenli lncRNA 为肢体特异性 En1 调控因子。
Nature. 2021 Apr;592(7852):93-98. doi: 10.1038/s41586-021-03208-9. Epub 2021 Feb 10.
3
Exploiting the GTEx resources to decipher the mechanisms at GWAS loci.利用 GTEx 资源来破解 GWAS 位点的机制。
Genome Biol. 2021 Jan 26;22(1):49. doi: 10.1186/s13059-020-02252-4.
4
The GTEx Consortium atlas of genetic regulatory effects across human tissues.GTEx 联盟人类组织遗传调控效应图谱
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6
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Genome Biol. 2020 Sep 11;21(1):234. doi: 10.1186/s13059-020-02122-z.
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9
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10
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