美国斯坦福大学Stephen B. Montgomery、Olivia M. de Goede等研究人员合作揭示长非编码RNA与复杂疾病之间的联系。2021年4月16日，《细胞》杂志在线发表了这项研究成果。
研究人员表示，长非编码RNA（lncRNA）基因对分子和细胞功能具有公认的重要影响。然而，在成千上万的lncRNA基因中，鉴定具有疾病或性状相关性的亚群仍然是一项重大挑战。
为了系统地表征这些lncRNA基因，研究人员使用了基因型组织表达（GTEx）项目v8遗传和多组织转录组学数据，对49种组织中的14,100种lncRNA基因的表达、遗传调控、细胞环境和性状关联进行了分析。
使用这些方法，研究人员确定了1,432个lncRNA基因-性状关联，其中800个没有被邻近蛋白质编码基因的更强作用所解释。这包括了lncRNA定量性状基因座与炎症性肠病、1型和2型糖尿病与冠状动脉疾病之间的关联，以及与体重指数的罕见变异关联。
附：英文原文
Title: Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease
Author: Olivia M. de Goede, Daniel C. Nachun, Nicole M. Ferraro, Michael J. Gloudemans, Abhiram S. Rao, Craig Smail, Tiffany Y. Eulalio, Franois Aguet, Bernard Ng, Jishu Xu, Alvaro N. Barbeira, Stephane E. Castel, Sarah Kim-Hellmuth, YoSon Park, Alexandra J. Scott, Benjamin J. Strober, Shankara Anand, Stacey Gabriel, Gad A. Getz, Aaron Graubert, Kane Hadley, Robert E. Handsaker, Katherine H. Huang, Xiao Li, Daniel G. MacArthur, Samuel R. Meier, Jared L. Nedzel, Duyen T. Nguyen, Ayellet V. Segrè, Ellen Todres, Brunilda Balliu, Rodrigo Bonazzola, Andrew Brown, Donald F. Conrad, Daniel J. Cotter, Nancy Cox, Sayantan Das, Emmanouil T. Dermitzakis, Jonah Einson, Barbara E. Engelhardt, Eleazar Eskin, Elise D. Flynn, Laure Fresard, Eric R. Gamazon, Diego Garrido-Martín, Nicole R. Gay, Roderic Guigó, Andrew R. Hamel, Yuan He, Paul J. Hoffman, Farhad Hormozdiari, Lei Hou, Brian Jo, Silva Kasela, Seva Kashin, Manolis Kellis, Alan Kwong, Xin Li, Yanyu Liang, Serghei Mangul, Pejman Mohammadi, Manuel Muoz-Aguirre, Andrew B. Nobel, Meritxell Oliva, Yongjin Park, Princy Parsana, Ferran Reverter, John M. Rouhana, Chiara Sabatti, Ashis Saha, Matthew Stephens, Barbara E. Stranger, Nicole A. Teran, Ana Viuela, Gao Wang, Fred Wright, Valentin Wucher, Yuxin Zou, Pedro G. Ferreira, Gen Li, Marta Melé, Esti Yeger-Lotem, Debra Bradbury, Tanya Krubit, Jeffrey A. McLean, Liqun Qi, Karna Robinson, Nancy V. Roche, Anna M. Smith, David E. Tabor, Anita Undale, Jason Bridge, Lori E. Brigham, Barbara A. Foster, Bryan M. Gillard, Richard Hasz, Marcus Hunter, Christopher Johns, Mark Johnson, Ellen Karasik, Gene Kopen, William F. Leinweber, Alisa McDonald, Michael T. Moser, Kevin Myer, Kimberley D. Ramsey, Brian Roe, Saboor Shad, Jeffrey A. Thomas, Gary Walters, Michael Washington, Joseph Wheeler, Scott D. Jewell, Daniel C. Rohrer, Dana R. Valley, David A. Davis, Deborah C. Mash, Mary E. Barcus, Philip A. Branton, Leslie Sobin, Laura K. Barker, Heather M. Gardiner, Maghboeba Mosavel, Laura A. Siminoff
Issue&Volume: 2021-04-16
Abstract: Long non-coding RNA (lncRNA) genes have well-established and important impacts onmolecular and cellular functions. However, among the thousands of lncRNA genes, itis 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 genesacross 49 tissues for 101 distinct complex genetic traits. Using these approaches,we identified 1,432 lncRNA gene-trait associations, 800 of which were not explainedby stronger effects of neighboring protein-coding genes. This included associationsbetween lncRNA quantitative trait loci and inflammatory bowel disease, type 1 andtype 2 diabetes, and coronary artery disease, as well as rare variant associationsto body mass index.
DOI: 10.1016/j.cell.2021.03.050
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00381-0