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Cross-cohort analysis of expression and splicing quantitative trait loci in TOPMed.

Peter Orchard T. Blackwell L. Kachuri Peter J. Castaldi M. Cho S. Christenson P. Durda S. Gabriel C. Hersh S. Huntsman Seungyong Hwang R. Joehanes Mari Johnson Xingnan Li Honghuang Lin Ching-Ti Liu Yongmei Liu Angel C. Y. Mak A. Manichaikul David T. Paik A. Saferali Joshua D Smith K. Taylor Russell P. Tracy Jiongming Wang Mingqiang Wang J. Weinstock Jeffrey M Weiss H. Wheeler Yingxiao Zhou Sebastian Zöllner Joseph C. Wu L. Mestroni S. Graw Matthew R Taylor Victor E. Ortega W. C. Johnson Weiniu Gan Gonçalo R. Abecasis Deborah A Nickerson Namrata Gupta K. Ardlie Prescott G. Woodruff R. Bowler Deborah Meyers Alexander P. Reiner C. Kooperberg E. Ziv R. Vasan Martin G. Larson L. Cupples Edwin K. Silverman Stephen S. Rich N. Heard-Costa Hua Tang J. I. Rotter Albert V. Smith Daniel Levy F. Aguet Laura J. Scott L. Raffield Stephen C. J. Parker Namiko Abe L. Almasy S. Ament Pramod Anugu P. Auer D. Avramopoulos Adithya Balasubramanian R. Barr L. Barwick Terri H. Beaty Diane M. Becker Lewis C. Becker Amber Beitelshees Takis Benos Marcos Bezerra Joshua C. Bis J. Brody Ulrich Broeckel J. Broome Karen L. Bunting Erin J. Buth Vincent J. Carey C. Carty Richard Casaburi M. Chaffin Christy Chang Yi-Cheng Chang S. Chavan Bo-Juen Chen Wei-Min Chen S. Choi Lee-Ming Chuang Ren-Hua Chung M. Conomos Elaine Cornell C. Crandall J. Crapo Jeffrey L. Curtis Coleen Damcott S. David Lisa de las Fuentes P. D. de Vries R. Deka D. DeMeo S. Devine H. Dinh H. Doddapaneni Qing Duan R. Duggirala Charles B. Eaton L. Ekunwe A. El Boueiz L. Emery Charles R. Farber J. Farek N. Franceschini C. Frazar Mao Fu Stephanie M. Fullerton L. Fulton Shanshan Gao Yan Gao Margery L S Gass Heather Geiger Auyon J. Ghosh Chris Gignoux D. Glahn S. Gogarten Dao-Ping Gong H. Goring Daniel Grine C. Gu Y. Guan Michael N. Hall Yi Han Daniel N Harris Benjamin D. Heavner David M. Herrington B. Hobbs Elliott Hong Karin F. Hoth C. A. Hsiung Jianhong Hu Yi-Jen Hung H. Huston C. Hwu Rebecca D. Jackson D. Jain J. Johnsen R. Johnston Kimberly Jones Michael D. Kessler Alyna T. Khan Ziad M. Khan Wonji Kim J. Kimoff G. Kinney Holly Kramer C. Lange E. Lange C. Laurie C. Laurie M. LeBoff Sandra Lee Wen-Jane Lee David Levine J. Lewis Yun Li Xihong Lin Simin Liu Yu Liu Barry J. Make Alisa K. Manning J. Manson L. Martin M. Marton S. Mathai Susanne May P. McArdle Merry-Lynn N. McDonald Sean K. McFarland Daniel J. McGoldrick Caitlin P. McHugh Hao Mei J. Meigs Vipin K. Menon N. Min M. Moll Z. Momin M. Montasser J. Mychaleckyj R. Naik T. Naseri P. Natarajan Sarah C. Nelson Bonnie Neltner C. Nessner Osuji Nkechinyere J. O’Connell Tim O’Connor Heather M Ochs-Balcom Geoffrey O. Okwuonu James S. Pankow Cora Parker G. Peloso J. Peralta Marco V. Perez James A. Perry Ulrike Peters Lawrence S. Phillips Toni I. Pollin Julia Powers Becker M. Boorgula B. Psaty D. Qiao N. Rafaels M. Rajendran Laura J. Rasmussen-Torvik A. Ratan Robert M Reed Elizabeth A. Regan M. Reupena Rébecca Robillard C. Roselli Ingo Ruczinski Alexi Runnels Pamela H. Russell K. Ryan E. Sabino S. Salimi Sejal Salvi SL Salzberg K. Sandow J. Santibanez Karen L. Schwander Frank Sciurba F. Sériès A. Shetty A. Shetty Brian H. Silver Robert Skomro Tanja Smith S. Smoller B. Snively A. Stilp Garrett Storm E. Streeten J. Su Y. Sung Jody M Sylvia A. Szpiro M. Taub Simeon I. Taylor T. Thornton M. Threlkeld L. Tinker D. Tirschwell H. Tiwari Catherine Tong M. Tsai Dhananjay Vaidya Tarik Walker Robert B Wallace A. Walts Fei Wang Heming Wang K. Watson Jenn Watt L. Weng J. Wessel Kayleen Williams Carla Wilson James Wilson Lara Winterkorn Q. Wong Baojun Wu Huichun Xu Lisa R. Yanek Ivana V. Yang S. Zekavat Snow Xueyan Zhao Wei Zhao Xiaofeng Zhu
Jul 2026 · Science · Vol 393 6808, pp. eadx2989 · 0 citations · 101 references
Medicine

Abstract

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood (n = 6454) and lung (n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank-derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

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