Health Sciences and Medicine Faculty, Bond University, Robina, QLD, 4226, Australia.
Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, 4059, Australia.
Sci Rep. 2020 Jul 6;10(1):11089. doi: 10.1038/s41598-020-67870-1.
Mitochondria supply intracellular energy requirements during exercise. Specific mitochondrial haplogroups and mitochondrial genetic variants have been associated with athletic performance, and exercise responses. However, these associations were discovered using underpowered, candidate gene approaches, and consequently have not been replicated. Here, we used whole-mitochondrial genome sequencing, in conjunction with high-throughput genotyping arrays, to discover novel genetic variants associated with exercise responses in the Gene SMART (Skeletal Muscle Adaptive Response to Training) cohort (n = 62 completed). We performed a Principal Component Analysis of cohort aerobic fitness measures to build composite traits and test for variants associated with exercise outcomes. None of the mitochondrial genetic variants but eight nuclear encoded variants in seven separate genes were found to be associated with exercise responses (FDR < 0.05) (rs11061368: DIABLO, rs113400963: FAM185A, rs6062129 and rs6121949: MTG2, rs7231304: AFG3L2, rs2041840: NDUFAF7, rs7085433: TIMM23, rs1063271: SPTLC2). Additionally, we outline potential mechanisms by which these variants may be contributing to exercise phenotypes. Our data suggest novel nuclear-encoded SNPs and mitochondrial pathways associated with exercise response phenotypes. Future studies should focus on validating these variants across different cohorts and ethnicities.
线粒体在运动期间提供细胞内的能量需求。特定的线粒体单倍群和线粒体遗传变异与运动表现和运动反应有关。然而，这些关联是使用功率不足的候选基因方法发现的，因此尚未得到复制。在这里，我们使用全线粒体基因组测序，结合高通量基因分型阵列，在 Gene SMART（骨骼肌对训练的适应性反应）队列（n=62 例完成）中发现与运动反应相关的新遗传变异。我们对队列有氧健身测量值进行主成分分析，以构建复合特征并测试与运动结果相关的变体。除了八个核编码变异外，没有发现任何线粒体遗传变异与运动反应相关（FDR<0.05）（rs11061368：DIABLO，rs113400963：FAM185A，rs6062129 和 rs6121949：MTG2，rs7231304：AFG3L2，rs2041840：NDUFAF7，rs7085433：TIMM23，rs1063271：SPTLC2）。此外，我们概述了这些变体可能导致运动表型的潜在机制。我们的数据表明，与运动反应表型相关的新核编码 SNP 和线粒体途径。未来的研究应集中在不同队列和种族中验证这些变体。
