학술논문
Omics-driven investigation of the biology underlying intrinsic submaximal working capacity and its trainability.
Document Type
Academic Journal
Author
Hota M; Centre for Computational Biology, Duke-National University of Singapore Medical School, Singapore, Singapore.; Barber JL; Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, United States.; Ruiz-Ramie JJ; Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, United States.; Department of Kinesiology, Augusta University, Augusta, Georgia, United States.; Schwartz CS; Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, United States.; Lam DTUH; Centre for Computational Biology, Duke-National University of Singapore Medical School, Singapore, Singapore.; Rao P; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States.; Mi MY; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States.; Katz DH; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States.; Robbins JM; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States.; Clish CB; Metabolomics Platform, Broad Institute, Boston, Massachusetts, United States.; Gerszten RE; Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States.; Sarzynski MA; Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, United States.; Ghosh S; Centre for Computational Biology, Duke-National University of Singapore Medical School, Singapore, Singapore.; Bioinformatics Section, Human Genomics Core, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States.; Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore, Singapore.; Bouchard C; Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States.
Source
Publisher: American Physiological Society Country of Publication: United States NLM ID: 9815683 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1531-2267 (Electronic) Linking ISSN: 10948341 NLM ISO Abbreviation: Physiol Genomics Subsets: MEDLINE
Subject
Language
English
Abstract
Submaximal exercise capacity is an indicator of cardiorespiratory fitness with clinical and public health implications. Submaximal exercise capacity and its response to exercise programs are characterized by heritability levels of about 40%. Using physical working capacity (power output) at a heart rate of 150 beats/min (PWC150) as an indicator of submaximal exercise capacity in subjects of the HERITAGE Family Study, we have undertaken multi-omics and in silico explorations of the underlying biology of PWC150 and its response to 20 wk of endurance training. Our goal was to illuminate the biological processes and identify panels of genes associated with human variability in intrinsic PWC150 (iPWC150) and its trainability (dPWC150). Our bioinformatics approach was based on a combination of genome-wide association, skeletal muscle gene expression, and plasma proteomics and metabolomics experiments. Genes, proteins, and metabolites showing significant associations with iPWC150 or dPWC150 were further queried for the enrichment of biological pathways. We compared genotype-phenotype associations of emerging candidate genes with reported functional consequences of gene knockouts in mouse models. We investigated the associations between DNA variants and multiple muscle and cardiovascular phenotypes measured in HERITAGE subjects. Two panels of prioritized genes of biological relevance to iPWC150 (13 genes) and dPWC150 (6 genes) were identified, supporting the hypothesis that genes and pathways associated with iPWC150 are different from those underlying dPWC150. Finally, the functions of these genes and pathways suggested that human variation in submaximal exercise capacity is mainly driven by skeletal muscle morphology and metabolism and red blood cell oxygen-carrying capacity. NEW & NOTEWORTHY Multi-omics and in silico explorations of the genes and underlying biology of submaximal exercise capacity and its response to 20 wk of endurance training were undertaken. Prioritized genes were identified: 13 genes for variation in submaximal exercise capacity in the sedentary state and 5 genes for the response level to endurance training, with no overlap between them. Genes and pathways associated with submaximal exercise capacity in the sedentary state are different from those underlying trainability.