Cross-cohort analysis of expression and splicing quantitative trait loci in TOPMed
TOPMed 中表达和剪接数量性状位点的跨队列分析
Peter Orchard, Thomas W. Blackwell, Linda Kachuri, Peter J. Castaldi, Michael H. Cho, Stephanie A. Christenson, Peter Durda, Stacey Gabriel, Craig P. Hersh, Scott Huntsman, Seungyong Hwang, Roby Joehanes, Mari Johnson, Xingnan Li, Honghuang Lin, Ching-Ti Liu, Yongmei Liu, Angel C. Y. Mak, Ani W. Manichaikul, David T. Paik, Aabida Saferali, Joshua D. Smith, Kent D. Taylor, Russell P. Tracy, Jiongming Wang, Mingqiang Wang, Joshua S. Weinstock, Jeffrey Weiss, Heather E. Wheeler, Ying Zhou, Sebastian Zöllner, Joseph C. Wu, Luisa Mestroni, Sharon Graw, Matthew R. G. Taylor, Victor E. Ortega, W. Craig Johnson, Weiniu Gan, Goncalo Abecasis, Deborah A. Nickerson, Namrata Gupta, Kristin Ardlie, Prescott G. Woodruff, Russell P. Bowler, Deborah A. Meyers, Alex Reiner, Charles Kooperberg, Elad Ziv, Ramachandran S. Vasan, Martin G. Larson, L. Adrienne Cupples, Edwin K. Silverman, Stephen S. Rich, Nancy Heard-Costa, Hua Tang, Jerome I. Rotter, Albert V. Smith, Daniel Levy, NHLBI TOPMed Consortium Multi-Omics Working Group, NHLBI TOPMed Consortium§, François Aguet, Laura J. Scott, Laura M. Raffield, Stephen C. J. ParkerNamiko Abe, Laura Almasy, Seth Ament, Pramod Anugu, Paul Auer, Dimitrios Avramopoulos, Adithya Balasubramanian, R. Graham Barr, Lucas Barwick, Terri Beaty, Diane Becker, Lewis Becker, Amber Beitelshees, Takis Benos, Marcos Bezerra, Joshua Bis, Jennifer Brody, Ulrich Broeckel, Jai Broome, Karen Bunting, Erin Buth, Vincent Carey, Cara Carty, Richard Casaburi, Mark Chaffin, Christy Chang, Yi-Cheng Chang, Sameer Chavan, Bo-Juen Chen, Wei-Min Chen, Seung Hoan Choi, Lee-Ming Chuang, Ren-Hua Chung, Matthew Conomos, Elaine Cornell, Carolyn Crandall, James Crapo, Jeffrey Curtis, Coleen Damcott, Sean David, Lisa de las Fuentes, Paul de Vries, Ranjan Deka, Dawn DeMeo, Scott Devine, Huyen Dinh, Harsha Doddapaneni, Qing Duan, Ravi Duggirala, Charles Eaton, Lynette Ekunwe, Adel El Boueiz, Leslie Emery, Charles Farber, Jesse Farek, Nora Franceschini, Chris Frazar, Mao Fu, Stephanie M. Fullerton, Lucinda Fulton, Shanshan Gao, Yan Gao, Margery Gass, Heather Geiger, Auyon Ghosh, Chris Gignoux, David Glahn, Stephanie Gogarten, Da-Wei Gong, Harald Goring, Daniel Grine, C. Charles Gu, Yue Guan, Michael Hall, Yi Han, Daniel Harris, Ben Heavner, David Herrington, Brian Hobbs, Elliott Hong, Karin Hoth, Chao (Agnes) Hsiung, Jianhong Hu, Yi-Jen Hung, Haley Huston, Chii Min Hwu, Rebecca Jackson, Deepti Jain, Jill Johnsen, Rich Johnston, Kimberly Jones, Michael Kessler, Alyna Khan, Ziad Khan, Wonji Kim, John Kimoff, Greg Kinney, Holly Kramer, Christoph Lange, Ethan Lange, Cathy Laurie, Cecelia Laurie, Meryl LeBoff, Sandra Lee, Wen-Jane Lee, David Levine, Joshua Lewis, Yun Li, Xihong Lin, Simin Liu, Yu Liu, Barry Make, Alisa Manning, JoAnn Manson, Lisa Martin, Melissa Marton, Susan Mathai, Susanne May, Patrick McArdle, Merry-Lynn McDonald, Sean McFarland, Daniel McGoldrick, Caitlin McHugh, Hao Mei, James Meigs, Vipin Menon, Nancy Min, Matt Moll, Zeineen Momin, May Montasser, Josyf C Mychaleckyj, Rakhi Naik, Take Naseri, Pradeep Natarajan, Sarah C. Nelson, Bonnie Neltner, Caitlin Nessner, Osuji Nkechinyere, Jeff O'Connell, Tim O’Connor, Heather Ochs-Balcom, Geoffrey Okwuonu, James Pankow, Cora Parker, Gina Peloso, Juan Manuel Peralta, Marco Perez, James Perry, Ulrike Peters, Lawrence S Phillips, Toni Pollin, Julia Powers Becker, Meher Preethi Boorgula, Bruce Psaty, Dandi Qiao, Nicholas Rafaels, Mahitha Rajendran, Laura Rasmussen-Torvik, Aakrosh Ratan, Robert Reed, Elizabeth Regan, Muagututi‘a Sefuiva Reupena, Rebecca Robillard, Carolina Roselli, Ingo Ruczinski, Alexi Runnels, Pamela Russell, Kathleen Ryan, Ester Cerdeira Sabino, Shabnam Salimi, Sejal Salvi, Steven Salzberg, Kevin Sandow, Jireh Santibanez, Karen Schwander, Frank Sciurba, Frédéric Sériès, Amol Shetty, Aniket Shetty, Brian Silver, Robert Skomro, Tanja Smith, Sylvia Smoller, Beverly Snively, Adrienne M. Stilp, Garrett Storm, Elizabeth Streeten, Jessica Lasky Su, Yun Ju Sung, Jody Sylvia, Adam Szpiro, Margaret Taub, Simeon Taylor, Timothy A. Thornton, Machiko Threlkeld, Lesley Tinker, David Tirschwell, Hemant Tiwari, Catherine Tong, Michael Tsai, Dhananjay Vaidya, Tarik Walker, Robert Wallace, Avram Walts, Fei Fei Wang, Heming Wang, Karol Watson, Jennifer Watt, Lu-Chen Weng, Jennifer Wessel, Kayleen Williams, Carla Wilson, James Wilson, Lara Winterkorn, Quenna Wong, Baojun Wu, Huichun Xu, Lisa Yanek, Ivana Yang, Seyedeh Maryam Zekavat, Snow Xueyan Zhao, Wei Zhao, Xiaofeng Zhu
大多数与复杂性状相关的遗传变异被假设为调节基因表达。为了了解基因表达变异性背后的遗传学原理，我们对来自 Trans-Omics for Precision Medicine 项目的 14,324 个 RNA 测序样本进行了表征，并对六种组织和细胞类型（包括全血 (n = 6454) 和肺 (n = 1291)）进行了表达和剪接数量性状位点 (e/sQTL) 分析。我们检测到了数以万计的次级 cis-e/sQTL，表明次级 cis-e/sQTL 的发现仍然不饱和。我们对来自英国生物银行的 164 个性状的全基因组关联研究 (GWAS) 信号进行了精细绘图，并确定了 10,611 个 GWAS 信号的 e/sQTL 共定位，其中包括 7096 个与次级 e/sQTL 共定位的信号。我们的结果表明，即使是...