학술논문
Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease
Document Type
Report
Author
de Goede, Olivia M.; Nachun, Daniel C.; Ferraro, Nicole M.; Gloudemans, Michael J.; Rao, Abhiram S.; Smail, Craig; Eulalio, Tiffany Y.; Aguet, François; Ng, Bernard; Xu, Jishu; Barbeira, Alvaro N.; Castel, Stephane E.; Kim-Hellmuth, Sarah; Park, YoSon; Scott, Alexandra J.; Strober, Benjamin J.; Anand, Shankara; Gabriel, Stacey; Getz, Gad A.; Graubert, Aaron; Hadley, Kane; Handsaker, Robert E.; Huang, Katherine H.; Li, Xiao; MacArthur, Daniel G.; Meier, Samuel R.; Nedzel, Jared L.; Nguyen, Duyen T.; Segrè, Ayellet V.; Todres, Ellen; Balliu, Brunilda; Bonazzola, Rodrigo; Brown, Andrew; Conrad, Donald F.; Cotter, Daniel J.; Cox, Nancy; Das, Sayantan; Dermitzakis, Emmanouil T.; Einson, Jonah; Engelhardt, Barbara E.; Eskin, Eleazar; Flynn, Elise D.; Fresard, Laure; Gamazon, Eric R.; Garrido-Martín, Diego; Gay, Nicole R.; Guigó, Roderic; Hamel, Andrew R.; He, Yuan; Hoffman, Paul J.; Hormozdiari, Farhad; Hou, Lei; Jo, Brian; Kasela, Silva; Kashin, Seva; Kellis, Manolis; Kwong, Alan; Li, Xin; Liang, Yanyu; Mangul, Serghei; Mohammadi, Pejman; Muñoz-Aguirre, Manuel; Nobel, Andrew B.; Oliva, Meritxell; Park, Yongjin; Parsana, Princy; Reverter, Ferran; Rouhana, John M.; Sabatti, Chiara; Saha, Ashis; Stephens, Matthew; Stranger, Barbara E.; Teran, Nicole A.; Viñuela, Ana; Wang, Gao; Wright, Fred; Wucher, Valentin; Zou, Yuxin; Ferreira, Pedro G.; Li, Gen; Melé, Marta; Yeger-Lotem, Esti; Bradbury, Debra; Krubit, Tanya; McLean, Jeffrey A.; Qi, Liqun; Robinson, Karna; Roche, Nancy V.; Smith, Anna M.; Tabor, David E.; Undale, Anita; Bridge, Jason; Brigham, Lori E.; Foster, Barbara A.; Gillard, Bryan M.; Hasz, Richard; Hunter, Marcus; Johns, Christopher; Johnson, Mark; Karasik, Ellen; Kopen, Gene; Leinweber, William F.; McDonald, Alisa; Moser, Michael T.; Myer, Kevin; Ramsey, Kimberley D.; Roe, Brian; Shad, Saboor; Thomas, Jeffrey A.; Walters, Gary; Washington, Michael; Wheeler, Joseph; Jewell, Scott D.; Rohrer, Daniel C.; Valley, Dana R.; Davis, David A.; Mash, Deborah C.; Barcus, Mary E.; Branton, Philip A.; Sobin, Leslie; Barker, Laura K.; Gardiner, Heather M.; Mosavel, Maghboeba; Siminoff, Laura A.; Flicek, Paul; Haeussler, Maximilian; Juettemann, Thomas; Kent, W. James; Lee, Christopher M.; Powell, Conner C.; Rosenbloom, Kate R.; Ruffier, Magali; Sheppard, Dan; Taylor, Kieron; Trevanion, Stephen J.; Zerbino, Daniel R.; Abell, Nathan S.; Akey, Joshua; Chen, Lin; Demanelis, Kathryn; Doherty, Jennifer A.; Feinberg, Andrew P.; Hansen, Kasper D.; Hickey, Peter F.; Jasmine, Farzana; Jiang, Lihua; Kaul, Rajinder; Kibriya, Muhammad G.; Li, Jin Billy; Li, Qin; Lin, Shin; Linder, Sandra E.; Pierce, Brandon L.; Rizzardi, Lindsay F.; Skol, Andrew D.; Smith, Kevin S.; Snyder, Michael; Stamatoyannopoulos, John; Tang, Hua; Wang, Meng; Carithers, Latarsha J.; Guan, Ping; Koester, Susan E.; Little, A. Roger; Moore, Helen M.; Nierras, Concepcion R.; Rao, Abhi K.; Vaught, Jimmie B.; Volpi, Simona
Source
Cell. May 13, 2021, Vol. 184 Issue 10, 2633
Subject
Language
English
ISSN
0092-8674
Abstract
Keywords long non-coding RNA; lncRNA; expression quantitative trait loci; eQTL; co-expression; complex trait; disease; GTEx; colocalization Highlights * 29% of lncRNA genes with eQTLs show tissue-specific genetic regulation * Co-expression networks and single-cell data provide annotations for 94% of lncRNAs * Rare variants near lncRNA expression outliers impact complex traits, like BMI * We identify 800 lncRNA-trait relationships not explained by protein-coding genes Summary 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.