Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease

生物 基因 特质 数量性状位点 转录组 表达数量性状基因座 疾病 全基因组关联研究 计算生物学 人口 基因表达 长非编码RNA 遗传关联 核糖核酸 遗传学 基因型 单核苷酸多态性 医学 人口学 病理 社会学 计算机科学 程序设计语言
作者
Olivia M. de Goede,Daniel Nachun,Nicole M. Ferraro,Michael J. Gloudemans,Abhiram Rao,Craig Smail,Tiffany Eulalio,François Aguet,Bernard Ng,Jishu Xu,Alvaro Barbeira,Stephane E. Castel,Sarah Kim-Hellmuth,YoSon Park,Alexandra J. Scott,Benjamin J. Strober,Christopher D. Brown,Xiaoquan Wen,Ira M. Hall,Alexis Battle,Tuuli Lappalainen,Hae Kyung Im,Kristin Ardlie,Sara Mostafavi,Thomas Quertermous,Karla Kirkegaard,Stephen B. Montgomery,Shankara Anand,Stacey Gabriel,Gad Getz,Aaron Graubert,Kane Hadley,Robert E. Handsaker,Katherine 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 J. Cox,Sayantan Das,Emmanouil T. Dermitzakis,Jonah Einson,Barbara E. Engelhardt,Eleazar Eskin,Elise D. Flynn,Laure Frésard,Eric R. Gamazon,Diego Garrido-Martín,Nicole R. Gay,Roderic Guigó,Andrew R. Hamel,Yuan He,Paul Hoffman,Farhad Hormozdiari,Lei Hou,Brian Jo,Silva Kasela,Seva Kashin,M Kellis,Alan Kwong,Xin Li,Yanyu Liang,Serghei Mangul,Pejman Mohammadi,Manuel Muñoz-Aguirre,Andrew B. Nobel,Meritxell Oliva,Yong‐Jin Park,Princy Parsana,Ferrán Reverter,John M. Rouhana,Chiara Sabatti,Ashis Saha,Matthew Stephens,Barbara E. Stranger,Nicole A. Teran,Ana Viñuela,Gao Wang,Fred A. 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 Roche,Mark I. McCarthy,David E. Tabor,Anita H. Undale,Jason Bridge,Lori E. Brigham,Barbara A. Foster,Bryan M. Gillard,Richard Hasz,Marcus Hunter,Christopher Johns,Mark R. 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,J. Gary Wheeler,Scott D. Jewell,Daniel C. Rohrer,Dana R. Valley,David A. Davis,Deborah C. Mash,Mary E. Barcus,Philip A. Branton,Leslie H. Sobin,Laura K. Barker,Heather M. Gardiner,Maghboeba Mosavel,Laura A. Siminoff,Paul Flicek,Maximilian Haeussler,Thomas Juettemann,W. James Kent,Christopher M. Lee,Conner C. Powell,Kate R. Rosenbloom,Magali Ruffier,Dan Sheppard,Kieron Taylor,Stephen J. Trevanion,Daniel R. Zerbino,Nathan S. Abell,Joshua D. Smith,Lin Chen,Kathryn Demanelis,Jennifer A. Doherty,Andrew P. Feinberg,Kasper D. Hansen,Peter F. Hickey,Farzana Jasmine,Lihua Jiang,Rajinder Kaul,Muhammad G. Kibriya,Jin Billy Li,Qin Li,Shin Lin,Sandra E. Linder,Brandon L. Pierce,Lindsay F. Rizzardi,Andrew D. Skol,Kevin S. Smith,M Snyder,J Stamatoyannopoulos,Hua Tang,Meng Wang,Latarsha J. Carithers,Ping Guan,Susan E. Koester,Tzintzuni Garcia,Helen M. Moore,Concepcion R. Nierras,Abhi K. Rao,Jimmie B. Vaught,Simona Volpi
出处
期刊:Cell [Elsevier]
卷期号:184 (10): 2633-2648.e19 被引量:115
标识
DOI:10.1016/j.cell.2021.03.050
摘要

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.
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