Cell type–specific genetic regulation of gene expression across human tissues

Kim-Hellmuth, Sarah; Aguet, François; Oliva, Meritxell; Muñoz-Aguirre, Manuel; Kasela, Silva; Wucher, Valentin; Castel, Stephane E.; Hamel, Andrew R.; Viñuela, Ana; Roberts, Amy L.; Mangul, Serghei; Wen, Xiaoquan; Wang, Gao; Barbeira, Alvaro; Garrido-Martín, Diego; Nadel, Brian B.; Zou, Yuxin; Bonazzola, Rodrigo; Quan, Jie; Brown, Andrew; Martínez-Pérez, Ángel; Soria, José Manuel; Getz, Gad; Dermitzakis, Emmanouil T.; Small, Kerrin S.; Stephens, Matthew; Xi, Hualin Simon; Im, Hae Kyung; Guigó, Roderic; Segrè, Ayellet V.; Stranger, Barbara E.; Ardlie, Kristin; Lappalainen, Tuuli; Aguet, François; Anand, Shankara; Ardlie, Kristin; Gabriel, Stacey; Getz, Gad; Graubert, Aaron; Hadley, Kane; Handsaker, Robert E.; Huang, Katherine; Kashin, Seva; Li, Xiao; MacArthur, Daniel G.; Meier, Samuel R.; Nedzel, Jared L.; Nguyen, Duyen T.; Segrè, Ayellet V.; Todres, Ellen; Balliu, Brunilda; Barbeira, Alvaro; Battle, Alexis; Bonazzola, Rodrigo; Brown, Andrew; Brown, Christopher D.; Castel, Stephane E.; Conrad, Donald F.; Cotter, Daniel J.; Cox, Nancy J.; Das, Sayantan; Goede, Olivia M. de; Dermitzakis, Emmanouil T.; Einson, Jonah; Engelhardt, Barbara E.; Eskin, Eleazar; Eulalio, Tiffany; Ferraro, Nicole M.; Flynn, Elise D.; Frésard, Laure; Gamazon, Eric R.; Garrido-Martín, Diego; Gay, Nicole R.; Gloudemans, Michael J.; Guigó, Roderic; Hame, Andrew R.; He, Yuan; Hoffman, Paul; Hormozdiari, Farhad; Hou, Lei; Im, Hae Kyung; Jo, Brian; Kasela, Silva; Kellis, Manolis; Kim-Hellmuth, Sarah; Kwong, Alan; Lappalainen, Tuuli; Li, Xin; Liang, Yanyu; Mangul, Serghei; Mohammadi, Pejman; Montgomery, Stephen B.; Muñoz-Aguirre, Manuel; Nachun, Daniel; Nobel, Andrew B.; Oliva, Meritxell; Park, YoSon; Park, Yongjin; Parsana, Princy; Rao, Abhiram; Reverter, Ferrán; Rouhana, John M.; Sabatti, Chiara; Saha, Ashis; Stephens, Matthew; Stranger, Barbara E.; Strober, Benjamin J.; Teran, Nicole A.; Viñuela, Ana; Wang, Gao; Wen, Xiaoquan; Wright, Fred A.; Wucher, Valentin; Zou, Yuxin; Ferreira, Pedro G.; Li, Gen; Melé, Marta; Yeger‐Lotem, Esti; Barcus, Mary E.; Bradbury, Debra; Krubit, Tanya; McLean, Jeffrey A.; Qi, Liqun; Robinson, Karna; Roche, Nancy; Smith, Anna M.; Sobin, Leslie H.; Tabor, David E.; Undale, Anita H.; Bridge, Jason; Brigham, Lori E.; Foster, Barbara A.; Gillard, Bryan M.; Hasz, Richard; Hunter, Marcus Anthony; Johns, Christopher; Johnson, Mark P.; Karasik, Ellen; Kopen, Gene; Leinweber, William F.; McDonald, Alisa; Moser, Michael T.; Myer, Kevin; Ramsey, Kimberley D.; Roe, Brian; Shad, Saboor; Thomas, Jeffrey A.; Walters, Gary; Washington, Michael; Wheeler, J. Gary; Jewell, Scott D.; Rohrer, Daniel C.; Valley, Dana R.; Davis, David A.; Mash, Deborah C.; Branton, Philip A.; Barker, Laura K.; Gardiner, Heather M.; Mosavel, Maghboeba; Siminoff, Laura A.; Flicek, Paul; Haeussler, Maximilian; Juettemann, Thomas; Kent, W. James; Lee, Christopher M.; Powell, Conner C.; Rosenbloom, Kate R.; Ruffier, Magali; Sheppard, Dan; Taylor, Kieron; Trevanion, Stephen J.; Zerbino, Daniel R.; Abell, Nathan S.; Akey, Joshua M.; Chen, Lin; Demanelis, Kathryn; Doherty, Jennifer A.; Feinberg, Andrew P.; Hansen, Kasper D.; Hickey, Peter F.; Jasmine, Farzana; Jiang, Lihua; Kaul, Rajinder; Kibriya, Muhammad G.; Li, Jin Billy; Li, Qin; Lin, Shin; Linder, Sandra E.; Pierce, Brandon L.; Rizzardi, Lindsay F.; Skol, Andrew D.; Smith, Kevin S.; Snyder, M; Stamatoyannopoulos, J; Tang, Hua; Wang, Meng; Carithers, Latarsha J.; Guan, Ping; Koester, Susan E.; Little, A. Roger; Moore, Helen M.; Nierras, Concepcion R.; Rao, Abhi K.; Vaught, Jimmie B.; Volpi, Simona

doi:10.1126/science.aaz8528

articleScienceSep 10, 2020GREEN OA

Cell type–specific genetic regulation of gene expression across human tissues

SKSarah Kim-Hellmuth FAFrançois Aguet MOMeritxell Oliva MMManuel Muñoz-Aguirre SKSilva Kasela

Max Planck Institute of Psychiatry · New York Genome Center · +24 more institutions

PubMed

Indexed incrossrefpubmed

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…

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Topics & keywords

Topics

Keywords

Gene
Cell type
Biology
Gene expression
Cell
Genetics
Regulation of gene expression
Cell biology

UN Sustainable Development Goals

Zero hunger

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