Omics-driven investigation of the biology underlying intrinsic submaximal working capacity and its trainability.
Omics-driven investigation of the biology underlying intrinsic submaximal working capacity and its trainability.
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对内在次最大工作能力及其可训练性背后的生物学进行组学驱动的研究。
DOI：
10.1152/physiolgenomics.00163.2022
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发表时间：
2023
影响因子：
4.6
通讯作者：
Bouchard,Claude
中科院分区：
文献类型：
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作者：
Hota,Monalisa;Barber,JacobL;Ruiz-Ramie,JonathanJ;Schwartz,CharlesS;Lam,DoThuyUyenHa;Rao,Prashant;Mi,MichaelY;Katz,DanielH;Robbins,JeremyM;Clish,ClaryB;Gerszten,RobertE;Sarzynski,MarkA;Ghosh,Sujoy;Bouchard,Claude
次极量运动能力是一个具有临床和公共卫生意义的心肺适能指标。次极量运动能力及其对运动计划的反应的特征是遗传率约为40%。使用物理工作能力（功率输出）在150次/分钟的心率（PWC 150）作为次最大运动能力的指标，在受试者的遗产家庭研究，我们进行了多组学和在硅片上探索的潜在生物学PWC 150和它的反应，20周的耐力训练。我们的目标是阐明生物学过程，并确定与人类内在PWC 150（iPWC 150）及其可训练性（dPWC 150）相关的基因组。我们的生物信息学方法是基于全基因组关联、骨骼肌基因表达、血浆蛋白质组学和代谢组学实验的组合。进一步查询与iPWC 150或dPWC 150显著相关的基因、蛋白质和代谢产物，以富集生物学途径。我们在小鼠模型中比较了新兴候选基因的基因型-表型关联与基因敲除的功能后果。我们研究了遗传受试者中DNA变异与多种肌肉和心血管表型之间的相关性。确定了与iPWC 150（13个基因）和dPWC 150（6个基因）生物学相关的两组优先基因，支持与iPWC 150相关的基因和途径与dPWC 150相关的基因和途径不同的假设。最后，这些基因和途径的功能表明，人类的亚极量运动能力的变化主要是由骨骼肌形态和代谢以及红细胞携氧能力驱动的。新&值得注意的是，我们进行了亚极量运动能力及其对20周耐力训练的反应的基因和潜在生物学的多组学和计算机探索。鉴定优先化基因：13个基因在久坐状态下的次最大运动能力的变化和5个基因对耐力训练的反应水平，它们之间没有重叠。与久坐状态下的次极量运动能力相关的基因和途径与那些潜在的可训练性不同。https://apspublicationspodcast.podbean.com/e/omics-and-submaximal-work-capacity-and-trainability/
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 & NOTEWORTHYMulti-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.Listen to this article’s corresponding podcast at https://apspublicationspodcast.podbean.com/e/omics-and-submaximal-work-capacity-and-trainability/.