Genetic effects on gene expression across human tissues
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
Abstract
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.