The impact of exercise on gene regulation in association with complex trait genetics
Nikolai G. Vetr, Nicole R. Gay, MoTrPAC Study Group, Joshua N. Adkins, Brent G. Albertson, David Amar, Mary Anne S. Amper, Jose Juan Almagro Armenteros, Euan Ashley, Julian Avila-Pacheco, Dam Bae, Ali Tugrul Balci, Marcas Bamman, Nasim Bararpour, Elisabeth R. Barton, Pierre M. Jean Beltran, Bryan C. Bergman, Daniel H. Bessesen, Sue C. Bodine, Frank W. Booth, Brian Bouverat, Thomas W. Buford, Charles F. Burant, Tiziana Caputo, Steven Carr, Toby L. Chambers, Clarisa Chavez, Maria Chikina, Roxanne Chiu, Michael Cicha, Clary B. Clish, Paul M. Coen, Dan Cooper, Elaine Cornell, Gary Cutter, Karen P. Dalton, Surendra Dasari, Courtney Dennis, Karyn Esser, Charles R. Evans, Roger Farrar, Facundo M. Fernández, Kishore Gadde, Nicole Gagne, David A. Gaul, Yongchao Ge, Robert E. Gerszten, Bret H. Goodpaster, Laurie J. Goodyear, Marina A. Gritsenko, Kristy Guevara, Fadia Haddad, Joshua R. Hansen, Melissa Harris, Trevor Hastie, Krista M. Hennig, Steven G. Hershman, Andrea Hevener, Michael F. Hirshman, Zhenxin Hou, Fang-Chi Hsu, Kim M. Huffman, Chia-Jui Hung, Chelsea Hutchinson-Bunch, Anna A. Ivanova, Bailey E. Jackson, Catherine M. Jankowski, David Jimenez-Morales, Christopher A. Jin, Neil M. Johannsen, Robert L. Newton, Maureen T. Kachman, Benjamin G. Ke, Hasmik Keshishian, Wendy M. Kohrt, Kyle S. Kramer, William E. Kraus, Ian Lanza, Christiaan Leeuwenburgh, Sarah J. Lessard, Bridget Lester, Jun Z. Li, Malene E. Lindholm, Ana K. Lira, Xueyun Liu, Ching-ju Lu, Nathan S. Makarewicz, Kristal M. Maner-Smith, D. R. Mani, Gina M. Many, Nada Marjanovic, Andrea Marshall, Shruti Marwaha, Sandy May, Edward L. Melanson, Michael E. Miller, Matthew E. Monroe, Samuel G. Moore, Ronald J. Moore, Kerrie L. Moreau
Abstract
Endurance 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].