Genetic effects on gene expression across human tissues

作者：François Andrew A. Stephane E. Joe R. Yuan Brian Pejman YoS Aguet Brown Castel Davis He Jo Mohammadi Park Pars, François Andrew A. Stephane E. Joe R. Yuan Brian Pejman YoS Aguet Brown Castel Davis He Jo Mohammadi Park Pars, F. Aguet, A. Brown, S. Castel, Joe R. Davis, Yuan He, Brian Jo, P. Mohammadi, Yoson Park, P. Parsana, A. Segrè, B. Strober, Zachary Zappala, Beryl B. Ellen T. Kane Katherine H. Monkol Xiao Jared L. Cummings Gelfand Hadley Huang Lek Li Nedzel Nguyen, Beryl B. Cummings, Ellen T. Gelfand, Kane Hadley, Katherine H. Huang, M. Lek, Xiao Li, Jared L. Nedzel, Duyen Y. Nguyen, M. Noble, Timothy J. Sullivan, T. Tukiainen, D. MacArthur, Gad Getz, Anjene Ping Susan A. Roger Nicole C. Helen M. Abhi Jeffer Addington Guan Koester Little Lockhart Moore Rao S, A. Addington, P. Guan, Susan E. Koester, A. Little, N. Lockhart, Helen M. Moore, Abhi Rao, J. Struewing, S. Volpi, Lori E. Richard Marcus Christopher Mark Gene William F. Brigham Hasz Hunter Johns Johnson Kopen Leinweber, L. Brigham, R. Hasz, Marcus Hunter, Christopher Johns, Mark Johnson, G. Kopen, W. F. Leinweber, J. Lonsdale, Alisa McDonald, Bernadette Mestichelli, K. Myer, Brian Roe, Mike Salvatore, Saboor Shad, Jeffrey A. Thomas, Gary Walters, Michael Washington, Joseph Wheeler, J. Bridge, B. Foster, Bryan M. Gillard, Ellen Karasik, Rachna Kumar, Mark Miklos, M. T. Moser, Scott D. Jewell, Robert G. Montroy, D. Rohrer, Dana R. Valley, Deborah C. Mash, David A. Davis, Leslie Mary E. Philip A. Sobin Barcus Branton, L. Sobin, M. Barcus, P. Branton, Nathan S. Brunilda Olivier Laure Eric R. Diego Ariel D. H Abell Balliu Delaneau Frésard Gamazon Garrido-Mart, Nathan S. Abell, B. Balliu, O. Delaneau, Laure Frésard, E. Gamazon, D. Garrido-Martín, Ariel D. H. Gewirtz, Genna Gliner, Michael J. Gloudemans, Buhm Han, Amy Z. He, F. Hormozdiari, Xin Li, Boxiang Liu, E. Kang, Ian C. McDowell, H. Ongen, John Palowitch, Christine B. Peterson, G. Quon, S. Ripke, A. Saha, A. Shabalin, Tyler C. Shimko, J. Sul, Nicole A. Teran, Emily K. Tsang, Hailei Zhang, Yi-Hui Zhou, C. Bustamante, Nancy J. Cox, R. Guigó, M. Kellis, M. McCarthy, Don Conrad, E. Eskin, Gen Li, A. Nobel, C. Sabatti, Barbara E. Stranger, Xiaoquan Wen, Fred A. Wright, K. Ardlie, E. Dermitzakis, T. Lappalainen, François Kristin G. Beryl B. Ellen T. Gad Kane Robert E. Ka Aguet Ardlie Cummings Gelfand Getz Hadley Handsake, F. Aguet, K. Ardlie, Beryl B. Cummings, Ellen T. Gelfand, G. Getz, Kane Hadley, R. Handsaker, Katherine H. Huang, Seva Kashin, K. Karczewski, M. Lek, Xiao Li, D. MacArthur, Jared L. Nedzel, D. T. Nguyen, M. Noble, A. Segrè, Casandra A. Trowbridge, T. Tukiainen, Nathan S. Brunilda Ruth Omer Alexis Gireesh K. Andrew Chr Abell Balliu Barshir Basha Battle Bogu Brown Brown, Ruth Barshir, Omer Basha, A. Battle, G. Bogu, A. Brown, Christopher D. Brown, Lin S. Chen, Colby Chiang, Don Conrad, Nancy J. Cox, Farhan N. Damani, B. Engelhardt, E. Eskin, Pedro G. Ferreira, Laure Frésard, E. Gamazon, D. Garrido-Martín, Ariel D. H. Gewirtz, Genna Gliner, Michael J. Gloudemans, R. Guigó, I. Hall, Buhm Han, F. Hormozdiari, C. Howald, Hae Kyung Im, Brian Jo, Eun Yong Kang, Yungil Kim, Sarah Kim-Hellmuth, Boxiang Liu, S. Mangul, Ian C. McDowell, Jean Monlong, Stephen B. Montgomery, Manuel Muñoz-Aguirre, Anne W. Ndungu, Dan L. Nicolae, Meritxell Oliva, N. Panousis, Panagiotis K. Papasaikas, Yoson Park, Anthony J. Payne, J. Quan, F. Reverter, M. Sammeth, Alexandra J. Scott, A. Shabalin, Reza Sodaei, M. Stephens, Barbara E. Stranger, Sarah Urbut, M. van de Bunt, Gao Wang, Fred A. Wright, H. Xi, Esti Yeger-Lotem, J. Zaugg, Yi-Hui Zhou, Joshua M. Daniel Joanne Lin S. Melina Kathryn Morgan Jenn Akey Bates Chan Chen Claussnitzer Demanelis Diegel, J. Akey, Daniel Bates, Joanne Chan, M. Claussnitzer, Kathryn Demanelis, Morgan Diegel, J. Doherty, A. Feinberg, Maria S. Fernando, J. Halow, Kasper D. Hansen, E. Haugen, Peter F. Hickey, Lei Hou, F. Jasmine, Ruiqi Jian, Lihua Jiang, Audra K. Johnson, R. Kaul, M. Kellis, M. Kibriya, Kristen Lee, Jin Billy Li, Qin Li, Xiao Li, Jessica Lin, Shin Lin, Sandra Linder, C. Linke, Yaping Liu, Matthew T. Maurano, B. Molinie, Stephen B. Montgomery, Jemma Nelson, Fidencio J. Neri, Yongjin P. Park, B. Pierce, Nicola J. Rinaldi, L. Rizzardi, R. Sandstrom, Andrew D. Skol, Kevin S. Smith, Michael P. Snyder, J. Stamatoyannopoulos, Hua Tang, L. Wang, M. Wang, Nicholas Van Wittenberghe, Fan Wu, Rui Zhang, C. Nierras, Philip A. Latarsha J. Ping Helen M. Abhi Jimmie B. Branton Carithers Guan Moore Rao Vaught, P. Branton, Latarsha J. Carithers, P. Guan, Helen M. Moore, Abhi Rao, J. Vaught, Sarah E. Nicole C. Casey Jeffery P. Simona Gould Lockart Martin Struewing Volpi, Sarah E. Gould, Nicole C. Lockart, Casey Martin, J. Struewing, S. Volpi, Anjene M. Susan E. Addington Koester, A. Addington, Susan E. Koester, A. Little, Lori E. Richard Marcus Christopher Mark Gene William F. Brigham Hasz Hunter Johns Johnson Kopen Leinweber, L. Brigham, Mark Johnson, Brian Roe, Gary Walters, Michael Washington, Jason Barbara A. Bryan M. Ellen Rachna Mark Michael T. Bridge Foster Gillard Karasik Kumar Miklos Moser, Scott D. Robert G. Daniel C. Dana R. Jewell Montroy Rohrer Valley, Scott D. Jewell, Robert G. Montroy, D. Rohrer, Dana R. Valley, David A. Deborah C. Davis Mash, David A. Davis, Deborah C. Mash, Anita H. Anna M. David E. Nancy V. Jeffrey A. Negin Karn Undale Smith Tabor Roche McLean Vatanian Robinson, Anita H. Undale, Anna M. Smith, D. Tabor, Nancy V. Roche, J. McLean, Negin Vatanian, Karna L. Robinson, L. Sobin, M. Barcus, Kimberly M. Valentino, L. Qi, Steven Hunter, P. Hariharan, Shilpi Singh, K. S. Um, Takunda Matose, M. Tomaszewski, Laura K. Maghboeba Laura A. Heather M. Barker Mosavel Siminoff Traino, Laura K. Barker, M. Mosavel, L. Siminoff, H. Traino, Paul Thomas Magali Dan Kieron Stephen J. Daniel R. Flicek Juettemann Ruffier Sheppard Taylor Trevanio, Paul Flicek, Thomas Juettemann, Magali Ruffier, Daniel Sheppard, K. Taylor, S. Trevanion, D. Zerbino, Brian Mary Maximilian W. James Christopher M. Benedict K Craft Goldman Haeussler Kent Lee Paten Rosenbloom, B. Craft, M. Goldman, M. Haeussler, W. Kent, Christopher M. Lee, B. Paten, K. Rosenbloom, John Vivian, Jingchun Zhu · 发表于：Nature · 年份：2017 · DOI：10.1038/nature24277 · 被引用次数：3751 · 研究领域：Biology、Medicine

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.