Cell type–specific genetic regulation of gene expression across human tissues
Sarah Kim-Hellmuth(Max Planck Institute of Psychiatry), François Aguet(Broad Institute), Meritxell Oliva(Chicago Department of Public Health), Manuel Muñoz-Aguirre(Barcelona Institute of Science and Technology), Silva Kasela(New York Genome Center), Valentin Wucher(Barcelona Institute of Science and Technology), Stephane E. Castel(New York Genome Center), Andrew R. Hamel(Broad Institute), Ana Viñuela(University of Geneva), Amy L. Roberts(King's College London), Serghei Mangul(University of Southern California), Xiaoquan Wen(University of Michigan), Gao Wang(University of Chicago), Alvaro Barbeira(University of Chicago), Diego Garrido-Martín(Barcelona Institute of Science and Technology), Brian B. Nadel(University of California, Los Angeles), Yuxin Zou(University of Chicago), Rodrigo Bonazzola(University of Chicago), Jie Quan(Pfizer (United States)), Andrew Brown(University of Geneva), Ángel Martínez-Pérez(Hospital de Sant Pau), José Manuel Soria(Hospital de Sant Pau), Gad Getz(Broad Institute), Emmanouil T. Dermitzakis(University of Geneva), Kerrin S. Small(King's College London), Matthew Stephens(University of Chicago), Hualin Simon Xi(AbbVie (United States)), Hae Kyung Im(University of Chicago), Roderic Guigó(Universitat Pompeu Fabra), Ayellet V. Segrè(Broad Institute), Barbara E. Stranger(Northwestern University), Kristin Ardlie(Broad Institute), Tuuli Lappalainen(New York Genome Center), François Aguet(Broad Institute), Shankara Anand, Kristin Ardlie(Broad Institute), Stacey Gabriel, Gad Getz(Broad Institute), Aaron Graubert, Kane Hadley, Robert E. Handsaker, Katherine Huang, Seva Kashin, Xiao Li(New York Genome Center), Daniel G. MacArthur, Samuel R. Meier, Jared L. Nedzel, Duyen T. Nguyen, Ayellet V. Segrè(Broad Institute), Ellen Todres, Brunilda Balliu, Alvaro Barbeira(University of Chicago), Alexis Battle, Rodrigo Bonazzola(University of Chicago), Andrew Brown(University of Geneva), Christopher D. Brown(University of Geneva), Stephane E. Castel(New York Genome Center), Donald F. Conrad, Daniel J. Cotter, Nancy J. Cox, Sayantan Das, Olivia M. de Goede, Emmanouil T. Dermitzakis(University of Geneva), Jonah Einson, Barbara E. Engelhardt(Northwestern University), Eleazar Eskin, Tiffany Eulalio, Nicole M. Ferraro, Elise D. Flynn, Laure Frésard, Eric R. Gamazon, Diego Garrido-Martín(Barcelona Institute of Science and Technology), Nicole R. Gay, Michael J. Gloudemans, Roderic Guigó(Universitat Pompeu Fabra), Andrew R. Hame(Broad Institute), Yuan He(University of Chicago), Paul Hoffman, Farhad Hormozdiari, Lei Hou, Hae Kyung Im(University of Chicago), Brian Jo(Hospital de Sant Pau), Silva Kasela(New York Genome Center), Manolis Kellis, Sarah Kim-Hellmuth(Max Planck Institute of Psychiatry), Alan Kwong, Tuuli Lappalainen(New York Genome Center), Xin Li(New York Genome Center), Yanyu Liang, Serghei Mangul(University of Southern California), Pejman Mohammadi, Stephen B. Montgomery, Manuel Muñoz-Aguirre(Barcelona Institute of Science and Technology), Daniel Nachun, Andrew B. Nobel(University of Geneva), Meritxell Oliva(Chicago Department of Public Health), YoSon Park, Yongjin Park, Princy Parsana, Abhiram Rao, Ferrán Reverter, John M. Rouhana, Chiara Sabatti, Ashis Saha, Matthew Stephens(University of Chicago), Barbara E. Stranger(Northwestern University), Benjamin J. Strober, Nicole A. Teran, Ana Viñuela(University of Geneva), Gao Wang(University of Chicago), Xiaoquan Wen(University of Michigan), Fred A. Wright, Valentin Wucher(Barcelona Institute of Science and Technology), Yuxin Zou(University of Chicago), Pedro G. Ferreira, Gen Li(New York Genome Center), Marta Melé, Esti Yeger‐Lotem, Mary E. Barcus, Debra Bradbury, Tanya Krubit, Jeffrey A. McLean, Liqun Qi, Karna Robinson, Nancy Roche, Anna M. Smith, Leslie H. Sobin, David E. Tabor, Anita H. Undale, Jason Bridge, Lori E. Brigham, Barbara A. Foster(Northwestern University), 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(University of California, Los Angeles), 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, W. James 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(AbbVie (United States)), 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(New York Genome Center), Qin Li(New York Genome Center), Shin Lin(AbbVie (United States)), Sandra E. Linder, Brandon L. Pierce, Lindsay F. Rizzardi, Andrew D. Skol, Kevin S. Smith, M Snyder, J Stamatoyannopoulos, Hua Tang(AbbVie (United States)), Meng Wang(University of Chicago), 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
Cited by 584Open Access
Abstract
The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci in cis (QTLs) for the majority of genes across a wide range of human tissues. However, the functional characterization of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. We mapped interactions between computational estimates of cell type abundance and genotype to identify cell type-interaction QTLs for seven cell types and show that cell type-interaction expression QTLs (eQTLs) provide finer resolution to tissue specificity than bulk tissue cis-eQTLs. Analyses of genetic associations with 87 complex traits show a contribution from cell type-interaction QTLs and enables the discovery of hundreds of previously unidentified colocalized loci that are masked in bulk tissue.