TY - JOUR T1 - Local genetic effects on gene expression across 44 human tissues JF - bioRxiv DO - 10.1101/074450 SP - 074450 AU - François Aguet AU - Andrew A. Brown AU - Stephane E. Castel AU - Joe R. Davis AU - Pejman Mohammadi AU - Ayellet V. Segrè AU - Zachary Zappala AU - Nathan S. Abell AU - Laure Frésard AU - Eric R. Gamazon AU - Ellen Gelfand AU - Michael J. Gloudemans AU - Yuan He AU - Farhad Hormozdiari AU - Xiao Li AU - Xin Li AU - Boxiang Liu AU - Diego Garrido-Martín AU - Halit Ongen AU - John J. Palowitch AU - YoSon Park AU - Christine B. Peterson AU - Gerald Quon AU - Stephan Ripke AU - Andrey A. Shabalin AU - Tyler C. Shimko AU - Benjamin J. Strober AU - Timothy J. Sullivan AU - Nicole A. Teran AU - Emily K. Tsang AU - Hailei Zhang AU - Yi-Hui Zhou AU - Alexis Battle AU - Carlos D. Bustamonte AU - Nancy J. Cox AU - Barbara E. Engelhardt AU - Eleazar Eskin AU - Gad Getz AU - Manolis Kellis AU - Gen Li AU - Daniel G. MacArthur AU - Andrew B. Nobel AU - Chiara Sabbati AU - Xiaoquan Wen AU - Fred A. Wright AU - GTEx Consortium AU - Tuuli Lappalainen AU - Kristin G. Ardlie AU - Emmanouil T. Dermitzakis AU - Christopher D. Brown AU - Stephen B. Montgomery Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/09/09/074450.abstract N2 - Expression quantitative trait locus (eQTL) mapping provides a powerful means to identify functional variants influencing gene expression and disease pathogenesis. We report the identification of cis-eQTLs from 7,051 post-mortem samples representing 44 tissues and 449 individuals as part of the Genotype-Tissue Expression (GTEx) project. We find a cis-eQTL for 88% of all annotated protein-coding genes, with one-third having multiple independent effects. We identify numerous tissue-specific cis-eQTLs, highlighting the unique functional impact of regulatory variation in diverse tissues. By integrating large-scale functional genomics data and state-of-the-art fine-mapping algorithms, we identify multiple features predictive of tissue-specific and shared regulatory effects. We improve estimates of cis-eQTL sharing and effect sizes using allele specific expression across tissues. Finally, we demonstrate the utility of this large compendium of cis-eQTLs for understanding the tissue-specific etiology of complex traits, including coronary artery disease. The GTEx project provides an exceptional resource that has improved our understanding of gene regulation across tissues and the role of regulatory variation in human genetic diseases. ER -