Genetic effects on gene expression across human tissues

著者: Eric Haugen, Yuan He, Lin Chen, Emmanouil T. Dermitzakis, Philip A. Branton, Andrew B. Nobel, YoSon Park, Jeffrey A. McLean, Fidencio Neri, David E. Tabor, Ashis Saha, Leslie H. Sobin, Jennifer A. Doherty, Kate R. Rosenbloom, Jie Quan, Benjamin J. Strober, Yaping Liu, Dana R. Valley, Omer Basha, Ruth Barshir, Casandra A. Trowbridge, Ayellet V. Segrè, Andrew D. Skol, Ellen Karasik, Jason Bridge, Wm. Kent, Colby Chiang, Farhan N. Damani, Konrad J. Karczewski, Mary E. Barcus, Meritxell Oliva, Panagiotis Papasaikas, Jemma Nelson, Caroline Linke, Benedict Paten, Ellen Gelfand, Jingchun Zhu, Fred A. Wright, Kevin S. Smith, Jessica Halow, Sarah Kim-Hellmuth, Michael F. Salvatore, Steven Hunter, Michael S. Noble, Mary J. Goldman, Duyen Y. Nguyen, Shilpi Singh, Daniel C. Rohrer, Nancy J. Cox, Peter F. Hickey, Alexis Battle, Melina Claussnitzer, Benoit Molinié, François Aguet, Brunilda Balliu, Jeffrey A. Thomas, Farhad Hormozdiari, Lei Hou, Rajinder Kaul, Christine B. Peterson, W. Marston Linehan, Laura K. Barker, Christopher Brown, Ping Guan, Kristen Lee, Michael J. Gloudemans, Stephan Ripke, Michael T. Moser, Manuel Muñoz-Aguirre, Maximilian Haeussler, Negin Vatanian, Ariel DH Gewirtz, Stephane E. Castel, Jean Monlong, Alexandra J. Scott, J Stamatoyannopoulos, Magali Ruffier, Zachary Zappala, Xiao Li, Pedro G. Ferreira, Concepcion R. Nierras, Esti Yeger‐Lotem, Xiaoquan Wen, Jeffery P. Struewing, Olivier Delaneau, Taru Tukiainen, M. Tomaszewski, Brian Jo, Yong‐Jin Park, Casey Martin, Gireesh K. Bogu, Brandon L. Pierce, Yi‐Hui Zhou, Eleazar Eskin, Ferrán Reverter, Roderic Guigó, Nicole A. Teran, Monkol Lek, William F. Leinweber, Kristin Ardlie, Gene Kopen, Halit Ongen, John T. Lonsdale, Ira M. Hall, Carlos D. Bustamante, Gerald Quon, Buhm Han, Pejman Mohammadi, Dan L. Nicolae, Manolis Kellis, John Vivian, Karna Robinson, David A. Davis, Michael Washington, Robert G. Montroy, Brian Craft, Gao Wang, Diego Garrido-Martín, Kieron Taylor, Sandra M. Linder, Kane Hadley, Addington, Anjene M., Joe R. Davis, Laura A. Siminoff, Mark Miklos, Emily K. Tsang, Morgan Diegel, Deborah C. Mash, Ian C. McDowell, Nicole C. Lockhart, A. J. Payne, Nathan S. Abell, Beryl B. Cummings, J. Gary Wheeler, Takunda Matose, Kathryn Demanelis, Genna Gliner, Matthew Stephens, Alisa McDonald, Abhi Rao, Barbara A. Foster, Laure Frésard, Andrew Brown, Rui Zhang, Nicola J. Rinaldi, Bryan M. Gillard, Daniel R. Zerbino, Chiara Sabatti, Helen M. Moore, Richard Hasz, Lori E. Brigham, Judith B. Zaugg, Ruiqi Jian, Donald F. Conrad, M Snyder, Hae Kyung Im, Fan Wu, Daniel G. MacArthur, Boxiang Liu, Eric R. Gamazon, Lihua Jiang, Michael Sammeth, Christopher Johns, Matthew T. Maurano, Kasper D. Hansen, Eun Yong Kang, Kevin Myer, Hua Tang, Mark P. Johnson, Marian S. Fernando, Anna Marie Smith, Sarah Urbut, Sarah E. Gould, Nicholas Van Wittenberghe, Christopher M. Lee, Barbara E. Engelhardt, Nikolaos Panousis, John Palowitch, Muhammad G. Kibriya, Dan Sheppard, Mark I. McCarthy, Anne W. Ndungu, Kimberly M. Valentino, Reza Sodaei, Richard Sandstrom, Princy Parsana, Yungil Kim, Rachna Kumar, Joanne Chan, A. Roger Little, Tyler C. Shimko, Simona Volpi, Qin Li, Joshua M. Akey, Gary Walters, Bryan Roe, Anita H. Undale, Martijn van de Bunt, Addington, Anjene M., Gad Getz, Jin Billy Li, Serghei Mangul, Andrew P. Feinberg, Jae Hoon Sul, Lindsay F. Rizzardi, Duyen T. Nguyen, Barbara E. Stranger, Ki Sung Um, Paul Flicek, Stephen J. Trevanion, Jimmie B. Vaught, Nicole C. Lockart, Jared L. Nedzel, Robert E. Handsaker, Marcus Anthony Hunter, Hualin Simon Xi, Daniel J. Bates, Cédric Howald, Nancy Roche, Susan E. Koester, Katherine Huang, Timothy J. Sullivan, Meng Wang, Andrey A. Shabalin, Saboor Shad, Pushpa Hariharan, Amy Z. He, Liqun Qi, Tuuli Lappalainen, Xin Li, Latarsha J. Carithers, Bernadette Mestichelli, Seva Kashin, Gen Li, Farzana Jasmine, Thomas Juettemann, Stephen B. Montgomery, Hailei Zhang, Heather M. Traino, Maghboeba Mosavel, Susan E. Koester, Shin Lin, Scott D. Jewell, Audra Johnson, Li Wang - 2020 被引用: 62

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.