Determinants of telomere length across human tissues

著者: Kathryn Demanelis, Farzana Jasmine, Lin Chen, Meytal Chernoff, Tong Lin, Dayana Delgado, Chenan Zhang, Justin Shinkle, Mekala Sabarinathan, Hannah Lin, Eduardo Ramirez, Meritxell Oliva, Sarah Kim-Hellmuth, Barbara E. Stranger, Tsung‐Po Lai, Abraham Aviv, Kristin Ardlie, François Aguet, Habibul Ahsan, Jennifer A. Doherty, Muhammad G. Kibriya, Brandon L. Pierce, François Aguet, Shankara Anand, Kristin Ardlie, Stacey Gabriel, Gad Getz, Aaron Graubert, Kane Hadley, Robert E. Handsaker, Katherine Huang, Seva Kashin, Xiao Li, Daniel G. MacArthur, Samuel R. Meier, Jared L. Nedzel, Duyen T. Nguyen, Ayellet V. Segrè, Ellen Todres, Brunilda Balliu, Alvaro Barbeira, Alexis Battle, Rodrigo Bonazzola, Andrew Brown, Christopher Brown, Stephane E. Castel, Donald F. Conrad, Daniel J. Cotter, Nancy J. Cox, Sayantan Das, Olivia M. de Goede, Emmanouil T. Dermitzakis, Jonah Einson, Barbara E. Engelhardt, Eleazar Eskin, Tiffany Eulalio, Nicole M. Ferraro, Elise D. Flynn, Laure Frésard, Eric R. Gamazon, Diego Garrido-Martín, Nicole R. Gay, Michael J. Gloudemans, Roderic Guigó, Andrew R. Hame, Yuan He, Paul Hoffman, Farhad Hormozdiari, Lei Hou, Hae Kyung Im, Brian Jo, Silva Kasela, Manolis Kellis, Sarah Kim-Hellmuth, Alan Kwong, Tuuli Lappalainen, Xin Li, Yanyu Liang, Serghei Mangul, Pejman Mohammadi, Stephen B. Montgomery, Manuel Muñoz-Aguirre, Daniel Nachun, Andrew B. Nobel, Meritxell Oliva, YoSon Park, Yongjin Park, Princy Parsana, Abhiram Rao, Ferrán Reverter, John M. Rouhana, Chiara Sabatti, Ashis Saha, Matthew Stephens, Barbara E. Stranger, Benjamin J. Strober, Nicole A. Teran, Ana Viñuela, Gao Wang, Xiaoquan Wen, Fred A. Wright, Valentin Wucher, Yuxin Zou, Pedro G. Ferreira, Gen Li, Marta Melé, Esti Yeger‐Lotem, Mary E. Barcus, Debra Bradbury, Tanya Krubit, Jeffrey A. McLean, Liqun Qi, Karna Robinson, Nancy Roche, Anna Marie Smith, Leslie H. Sobin, David E. Tabor, Anita H. Undale, Jason Bridge, Lori E. Brigham, Barbara A. Foster, Bryan M. Gillard, Richard Hasz, Marcus Anthony Hunter, Christopher Johns, Mark P. 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, Philip A. Branton, Laura K. Barker, Heather M. Gardiner, Maghboeba Mosavel, Laura A. Siminoff, Paul Flicek, Maximilian Haeussler, Thomas Juettemann, Wm. 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 M. Akey, 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, Li Qin, Shin Lin, Sandra E. Linder, Brandon L. Pierce, Lindsay F. Rizzardi, Andrew D. Skol, Kevin S. Smith, M Snyder, J Stamatoyannopoulos, Hua Tang, Meng C. Wang, Latarsha J. Carithers, Ping Guan, Susan E. Koester, A. Roger Little, Helen M. Moore, Concepcion R. Nierras, Abhi K. Rao, Jimmie B. Vaught, Simona Volpi - Science 2020 被引用: 497

Telomere shortening is a hallmark of aging. Telomere length (TL) in blood cells has been studied extensively as a biomarker of human aging and disease; however, little is known regarding variability in TL in nonblood, disease-relevant tissue types. Here, we characterize variability in TLs from 6391 tissue samples, representing >20 tissue types and 952 individuals from the Genotype-Tissue Expression (GTEx) project. We describe differences across tissue types, positive correlation among tissue types, and associations with age and ancestry. We show that genetic variation affects TL in multiple tissue types and that TL may mediate the effect of age on gene expression. Our results provide the foundational knowledge regarding TL in healthy tissues that is needed to interpret epidemiological studies of TL and human health.