The impact of exercise on gene regulation in association with complex trait genetics
Authors: Vetr Nikolai G. , Gay Nicole R. ,   MoTrPAC Study Group, Adkins Joshua N. , Albertson Brent G. , Amar David , Amper Mary Anne S. , Armenteros Jose Juan Almagro , Ashley Euan , Avila-Pacheco Julian , Bae Dam , Balci Ali Tugrul , Bamman Marcas , Bararpour Nasim , Barton Elisabeth R. , Jean Beltran Pierre M. , Bergman Bryan C. , Bessesen Daniel H. , Bodine Sue C. , Booth Frank W. , Bouverat Brian , Buford Thomas W. , Burant Charles F. , Caputo Tiziana , Carr Steven , Chambers Toby L. , Chavez Clarisa , Chikina Maria , Chiu Roxanne , Cicha Michael , Clish Clary B. , Coen Paul M. , Cooper Dan , Cornell Elaine , Cutter Gary , Dalton Karen P. , Dasari Surendra , Dennis Courtney , Esser Karyn , Evans Charles R. , Farrar Roger , Fernádez Facundo M. , Gadde Kishore , Gagne Nicole , Gaul David A. , Ge Yongchao , Gerszten Robert E. , Goodpaster Bret H. , Goodyear Laurie J. , Gritsenko Marina A. , Guevara Kristy , Haddad Fadia , Hansen Joshua R. , Harris Melissa , Hastie Trevor , Hennig Krista M. , Hershman Steven G. , Hevener Andrea , Hirshman Michael F. , Hou Zhenxin , Hsu Fang-Chi , Huffman Kim M. , Hung Chia-Jui , Hutchinson-Bunch Chelsea , Ivanova Anna A. , Jackson Bailey E. , Jankowski Catherine M. , Jimenez-Morales David , Jin Christopher A. , Johannsen Neil M. , Newton Robert L. , Kachman Maureen T. , Ke Benjamin G. , Keshishian Hasmik , Kohrt Wendy M. , Kramer Kyle S. , Kraus William E. , Lanza Ian , Leeuwenburgh Christiaan , Lessard Sarah J. , Lester Bridget , Li Jun Z. , Lindholm Malene E. , Lira Ana K. , Liu Xueyun , Lu Ching-ju , Makarewicz Nathan S. , Maner-Smith Kristal M. , Mani D. R. , Many Gina M. , Marjanovic Nada , Marshall Andrea , Marwaha Shruti , May Sandy , Melanson Edward L. , Miller Michael E. , Monroe Matthew E. , Moore Samuel G. , Moore Ronald J. , Moreau Kerrie L. , Mundorff Charles C. , Musi Nicolas , Nachun Daniel , Nair Venugopalan D. , Nair K. Sreekumaran , Nestor Michael D. , Nicklas Barbara , Nigro Pasquale , Nudelman German , Ortlund Eric A. , Pahor Marco , Pearce Cadence , Petyuk Vladislav A. , Piehowski Paul D. , Pincas Hanna , Powers Scott , Presby David M. , Qian Wei-Jun , Radom-Aizik Shlomit , Raja Archana Natarajan , Ramachandran Krithika , Ramaker Megan E. , Ramos Irene , Rankinen Tuomo , Raskind Alexander , Rasmussen Blake B. , Ravussin Eric , Rector R. Scott , Rejeski W. Jack , Richards Collyn Z-T. , Rirak Stas , Robbins Jeremy M. , Rooney Jessica L. , Rubenstein Aliza B. , Ruf-Zamojski Frederique , Rushing Scott , Sagendorf Tyler J. , Samdarshi Mihir , Sanford James A. , Savage Evan M. , Schauer Irene E. , Schenk Simon , Schwartz Robert S. , Sealfon Stuart C. , Seenarine Nitish , Smith Kevin S. , Smith Gregory R. , Snyder Michael P. , Soni Tanu , Oliveira De Sousa Luis Gustavo , Sparks Lauren M. , Steep Alec , Stowe Cynthia L. , Sun Yifei , Teng Christopher , Thalacker-Mercer Anna , Thyfault John , Tibshirani Rob , Tracy Russell , Trappe Scott , Trappe Todd A. , Uppal Karan , Vangeti Sindhu , Vasoya Mital , Volpi Elena , Vornholt Alexandria , Walkup Michael P. , Walsh Martin J. , Wheeler Matthew T. , Williams John P. , Wu Si , Xia Ashley , Yan Zhen , Yu Xuechen , Zang Chongzhi , Zaslavsky Elena , Zebarjadi Navid , Zhang Tiantian , Zhao Bingqing , Zhen Jimmy , Montgomery Stephen B. 
Published: May 2024

AbstractEndurance exercise training is known to reduce risk for a range of complex diseases. However, the molecular basis of this effect has been challenging to study and largely restricted to analyses of either few or easily biopsied tissues. Extensive transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium has provided a unique opportunity to clarify how exercise can affect tissue-specific gene expression and further suggest how exercise adaptation may impact complex disease-associated genes. To build this map, we integrate this multi-tissue atlas of gene expression changes with gene-disease targets, genetic regulation of expression, and trait relationship data in humans. Consensus from multiple approaches prioritizes specific tissues and genes where endurance exercise impacts disease-relevant gene expression. Specifically, we identify a total of 5523 trait-tissue-gene triplets to serve as a valuable starting point for future investigations [Exercise; Transcription; Human Phenotypic Variation].