Functional partitioning of local and distal gene expression regulation in multiple human tissues
作者： Xuanyao Liu , Hilary K. Finucane , Alexander Gusev , Gaurav Bhatia , Steven Gazal
DOI: 10.1101/046383
关键词:
摘要: Studies of the genetics gene expression have served as a key tool for linking genetic variants to phenotypes. Large-scale eQTL mapping studies identified large number local eQTLs, but molecular mechanism how regulate is still unclear, particularly distal which these are not well-powered detect. In this study, we use heritability partitioning approach dissect functional components regulation. We make an existing method, stratified LD score regression, that leverages all (not just those pass stringent significance thresholds) partition across categories, and extend method in 15 human tissues. The top enriched categories regulation peripheral blood included super enhancers (5.18x), coding regions (3.73x), conserved (2.33x) four histone marks (p<3x10-7 enrichments); enrichments were similar also observed substantial expression: (1.91x), (4.47x), (4.51x) two enrichments). Analyses correlation tissues showed largely shared tissues, highly tissue-specific. Our results elucidate architecture
sci-hub.st 参考文章(48)
GTEx Consortium, Kristin G Ardlie, David S Deluca, Ayellet V Segrè, Timothy J Sullivan, Taylor R Young, Ellen T Gelfand, Casandra A Trowbridge, Julian B Maller, Taru Tukiainen, Monkol Lek, Lucas D Ward, Pouya Kheradpour, Benjamin Iriarte, Yan Meng, Cameron D Palmer, Tõnu Esko, Wendy Winckler, Joel N Hirschhorn, Manolis Kellis, Daniel G MacArthur, Gad Getz, Andrey A Shabalin, Gen Li, Yi-Hui Zhou, Andrew B Nobel, Ivan Rusyn, Fred A Wright, Tuuli Lappalainen, Pedro G Ferreira, Halit Ongen, Manuel A Rivas, Alexis Battle, Sara Mostafavi, Jean Monlong, Michael Sammeth, Marta Mele, Ferran Reverter, Jakob M Goldmann, Daphne Koller, Roderic Guigó, Mark I McCarthy, Emmanouil T Dermitzakis, Eric R Gamazon, Hae Kyung Im, Anuar Konkashbaev, Dan L Nicolae, Nancy J Cox, Timothée Flutre, Xiaoquan Wen, Matthew Stephens, Jonathan K Pritchard, Zhidong Tu, Bin Zhang, Tao Huang, Quan Long, Luan Lin, Jialiang Yang, Jun Zhu, Jun Liu, Amanda Brown, Bernadette Mestichelli, Denee Tidwell, Edmund Lo, Mike Salvatore, Saboor Shad, Jeffrey A Thomas, John T Lonsdale, Michael T Moser, Bryan M Gillard, Ellen Karasik, Kimberly Ramsey, Christopher Choi, Barbara A Foster, John Syron, Johnell Fleming, Harold Magazine, Rick Hasz, Gary D Walters, Jason P Bridge, Mark Miklos, Susan Sullivan, Laura K Barker, Heather M Traino, Maghboeba Mosavel, Laura A Siminoff, Dana R Valley, Daniel C Rohrer, Scott D Jewell, Philip A Branton, Leslie H Sobin, Mary Barcus, Liqun Qi, Jeffrey McLean, Pushpa Hariharan, Ki Sung Um, Shenpei Wu, David Tabor, Charles Shive, Anna M Smith, Stephen A Buia, Anita H Undale, Karna L Robinson, Nancy Roche, Kimberly M Valentino, Angela Britton, Robin Burges, Debra Bradbury, Kenneth W Hambright, John Seleski, Greg E Korzeniewski, Kenyon Erickson, Yvonne Marcus, Jorge Tejada, Mehran Taherian, Chunrong Lu, Margaret Basile, Deborah C Mash, Simona Volpi, Jeffery P Struewing, Gary F Temple, Joy Boyer, Deborah Colantuoni, Roger Little, Susan Koester, Latarsha J Carithers, Helen M Moore, Ping Guan, Carolyn Compton, Sherilyn J Sawyer, Joanne P Demchok, Jimmie B Vaught, Chana A Rabiner, Nicole C Lockhart, Kristin G Ardlie, Gad Getz, Fred A Wright, Manolis Kellis, Simona Volpi, Emmanouil T Dermitzakis, None, The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans Science. ,vol. 348, pp. 648- 660 ,(2015) , 10.1126/SCIENCE.1262110
Halit Ongen, Emmanouil T. Dermitzakis, Alternative Splicing QTLs in European and African Populations American Journal of Human Genetics. ,vol. 97, pp. 567- 575 ,(2015) , 10.1016/J.AJHG.2015.09.004
Hilary K Finucane, Brendan Bulik-Sullivan, Alexander Gusev, Gosia Trynka, Yakir Reshef, Po-Ru Loh, Verneri Anttila, Han Xu, Chongzhi Zang, Kyle Farh, Stephan Ripke, Felix R Day, ReproGen Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Raci Consortium, Shaun Purcell, Eli Stahl, Sara Lindstrom, John RB Perry, Yukinori Okada, Soumya Raychaudhuri, Mark J Daly, Nick Patterson, Benjamin M Neale, Alkes L Price, None, Partitioning heritability by functional annotation using genome-wide association summary statistics Nature Genetics. ,vol. 47, pp. 1228- 1235 ,(2015) , 10.1038/NG.3404
Can Cenik, Elif Sarinay Cenik, Gun W. Byeon, Fabian Grubert, Sophie I. Candille, Damek Spacek, Bilal Alsallakh, Hagen Tilgner, Carlos L. Araya, Hua Tang, Emiliano Ricci, Michael P. Snyder, Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans Genome Research. ,vol. 25, pp. 1610- 1621 ,(2015) , 10.1101/GR.193342.115
Alexandra C. Nica, Leopold Parts, Daniel Glass, James Nisbet, Amy Barrett, Magdalena Sekowska, Mary Travers, Simon Potter, Elin Grundberg, Kerrin Small, Åsa K. Hedman, Veronique Bataille, Jordana Tzenova Bell, Gabriela Surdulescu, Antigone S. Dimas, Catherine Ingle, Frank O. Nestle, Paola di Meglio, Josine L. Min, Alicja Wilk, Christopher J. Hammond, Neelam Hassanali, Tsun-Po Yang, Stephen B. Montgomery, Steve O'Rahilly, Cecilia M. Lindgren, Krina T. Zondervan, Nicole Soranzo, Inês Barroso, Richard Durbin, Kourosh Ahmadi, Panos Deloukas, Mark I. McCarthy, Emmanouil T. Dermitzakis, Timothy D. Spector, , The architecture of gene regulatory variation across multiple human tissues: the MuTHER study PLOS Genetics. ,vol. 7, ,(2011) , 10.1371/JOURNAL.PGEN.1002003
Tuuli Lappalainen, Stephen B. Montgomery, Alexandra C. Nica, Emmanouil T. Dermitzakis, Epistatic selection between coding and regulatory variation in human evolution and disease. American Journal of Human Genetics. ,vol. 89, pp. 459- 463 ,(2011) , 10.1016/J.AJHG.2011.08.004
Alkes L. Price, Agnar Helgason, Gudmar Thorleifsson, Steven A. McCarroll, Augustine Kong, Kari Stefansson, Single-tissue and cross-tissue heritability of gene expression via identity-by-descent in related or unrelated individuals. PLOS Genetics. ,vol. 7, pp. 1- 9 ,(2011) , 10.1371/JOURNAL.PGEN.1001317
Frank W. Albert, Leonid Kruglyak, The role of regulatory variation in complex traits and disease Nature Reviews Genetics. ,vol. 16, pp. 197- 212 ,(2015) , 10.1038/NRG3891
A. B. Stergachis, E. Haugen, A. Shafer, W. Fu, B. Vernot, A. Reynolds, A. Raubitschek, S. Ziegler, E. M. LeProust, J. M. Akey, J. A. Stamatoyannopoulos, Exonic transcription factor binding directs codon choice and affects protein evolution Science. ,vol. 342, pp. 1367- 1372 ,(2013) , 10.1126/SCIENCE.1243490
Denes Hnisz, Brian J. Abraham, Tong Ihn Lee, Ashley Lau, Violaine Saint-André, Alla A. Sigova, Heather A. Hoke, Richard A. Young, Super-Enhancers in the Control of Cell Identity and Disease Cell. ,vol. 155, pp. 934- 947 ,(2013) , 10.1016/J.CELL.2013.09.053