Genetic effects on gene expression across human tissues

著者: François Aguet, Ayellet V. Segrè, Beryl B. Cummings, Ellen T. Gelfand, Kane Hadley, Katherine H. Huang, Monkol Lek, Xiao Li, Jared L. Nedzel, Duyen Y. Nguyen, Michael S. Noble, Timothy J. Sullivan, Taru Tukiainen, Daniel G. MacArthur, Gad Getz, Gerald Quon, Hailei Zhang, Manolis Kellis, Kristin G. Ardlie, Andrew A. Brown, Olivier Delaneau, Halit Ongen, Emmanouil T. Dermitzakis, Stephane E. Castel, Pejman Mohammadi, Tuuli Lappalainen, Joe R. Davis, Zachary Zappala, Nathan S. Abell, Tyler C. Shimko, Nicole A. Teran, Carlos D. Bustamante, Stephen B. Montgomery, Brunilda Balliu, Laure Frésard, Michael J. Gloudemans, Xin Li, Boxiang Liu, Emily K. Tsang, Yuan He, Benjamin J. Strober, Brian Jo, Ariel D. H. Gewirtz, YoSon Park, Christopher D. Brown, Princy Parsana, Amy Z. He, Ashis Saha, Alexis Battle, Stephan Ripke, Anjene Addington, Susan Koester, Ping Guan, Helen M. Moore, Abhi Rao, Philip A. Branton, A. Roger Little, Nicole C. Lockhart, Jeffery P. Struewing, Simona Volpi, Lori E. Brigham, Richard Hasz, Marcus Hunter, Kevin Myer, Bryan Roe, Christopher Johns, Joseph Wheeler, Mark Johnson, Gary Walters, Michael Washington, Gene Kopen, William F. Leinweber, John T. Lonsdale, Alisa McDonald, Bernadette Mestichelli, Michael Salvatore, Saboor Shad, Jeffrey A. Thomas, Jason Bridge, Mark Miklos, Barbara A. Foster, Bryan M. Gillard, Ellen Karasik, Rachna Kumar, Michael T. Moser, Scott D. Jewell, Robert G. Montroy, Daniel C. Rohrer, Dana Valley, Deborah C. Mash, David A. Davis, Leslie Sobin, Mary E. Barcus, Eric R. Gamazon, Nancy J. Cox, Diego Garrido-Martín, Roderic Guigó, Genna Gliner, Buhm Han, Farhad Hormozdiari, Eleazar Eskin, Eun Yong Kang, Ian C. McDowell, John J. Palowitch, Andrew B. Nobel, Christine B. Peterson, Andrey A. Shabalin, Jae Hoon Sul, Yi-Hui Zhou, Chiara Sabatti, Mark I. McCarthy, Donald F. Conrad, Gen Li, Barbara E. Stranger, Xiaoquan Wen, Fred A. Wright, Barbara E. Engelhardt, Robert E. Handsaker, Seva Kashin, Konrad J. Karczewski, Duyen T. Nguyen, Casandra A. Trowbridge, Melina Claussnitzer, Lei Hou, Yaping Liu, Benoit Molinie, Yongjin Park, Nicola J. Rinaldi, Li Wang, Nicholas Van Wittenberghe, Joanne Chan, Ruiqi Jian, Lihua Jiang, Jin Billy Li, Qin Li, Jessica Lin, Shin Lin, Sandra Linder, Kevin S. Smith, Michael P. Snyder, Hua Tang, Meng Wang, Rui Zhang, Ruth Barshir, Omer Basha, Esti Yeger-Lotem, Farhan N. Damani, Yungil Kim, Gireesh K. Bogu, Roderic Guigo, Jean Monlong, Manuel Muñoz-Aguirre, Panagiotis Papasaikas, Ferran Reverter, Reza Sodaei, Andrew Brown, Cedric Howald, Nikolaos Panousis, Sarah Kim-Hellmuth, Lin S. Chen, Kathryn Demanelis, Farzana Jasmine, Muhammad G. Kibriya, Brandon L. Pierce, Colby Chiang, Ira M. Hall, Alexandra J. Scott, Serghei Mangul, Pedro G. Ferreira, Ariel D.H. Gewirtz, Joshua M. Akey, Andrew P. Feinberg, Hae Kyung Im, Dan L. Nicolae, Meritxell Oliva, Marian S. Fernando, Caroline Linke, Andrew Skol, Fan Wu, Anne W. Ndungu, Anthony J. Payne, Martijn van de Bunt, Matthew Stephens, Sarah Urbut, Gao Wang, Jie Quan, Hualin S. Xi, Michael Sammeth, Judith B. Zaugg, Daniel Bates, Morgan Diegel, Jessica Halow, Eric Haugen, Audra Johnson, Rajinder Kaul, Kristen Lee, Jemma Nelson, Fidencio J. Neri, Richard Sandstrom, John Stamatoyannopoulos, Jennifer A. Doherty, Kasper D. Hansen, Lindsay F. Rizzardi, Peter F. Hickey, Matthew T. Maurano, Concepcion R. Nierras, Latarsha J. Carithers, Jimmie B. Vaught, Sarah E. Gould, Nicole C. Lockart, Casey Martin, Anjene M. Addington, Susan E. Koester, Brian Roe, Dana R. Valley, Anita H. Undale, Anna M. Smith, David E. Tabor, Nancy V. Roche, Jeffrey A. McLean, Negin Vatanian, Karna L. Robinson, Kimberly M. Valentino, Liqun Qi, Steven Hunter, Pushpa Hariharan, Shilpi Singh, Ki Sung Um, Takunda Matose, Maria M. Tomaszewski, Laura K. Barker, Laura A. Siminoff, Heather M. Traino, Maghboeba Mosavel, Paul Flicek, Thomas Juettemann, Magali Ruffier, Dan Sheppard, Kieron Taylor, Stephen J. Trevanion, Daniel R. Zerbino, Brian Craft, Mary Goldman, Maximilian Haeussler, W. James Kent, Christopher M. Lee, Benedict Paten, Kate R. Rosenbloom, John Vivian, Jingchun Zhu - Nature 2017 被引用: 4,727

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.