Low cardiorespiratory fitness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O2peak response following exercise training. Participant change in objectively measured V̇O2peak from 18 different interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n = 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms (SNPs) significantly associated (P < 1 × 10–5) with the magnitude of V̇O2peak response. Findings were tested in an independent validation study (n = 39) and compared to previous research. No variants at the genome-wide significance level were found after adjusting for key covariates (baseline V̇O2peak, individual study, principal components which were significantly associated with the trait). A Quantile–Quantile plot indicates there was minor inflation in the study. Twelve novel loci showed a trend of association with V̇O2peak response that reached suggestive significance (P < 1 × 10–5). The strongest association was found near the membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2) gene (rs6959961, P = 2.61 × 10–7). A PPS created from the 12 lead SNPs was unable to predict V̇O2peak response in a tenfold cross validation, or in an independent (n = 39) validation study (P > 0.1). Significant correlations were found for beta coefficients of variants in the Predict-HIIT (P < 1 × 10–4) and the validation study (P < × 10–6), indicating that general effects of the loci exist, and that with a higher statistical power, more significant genetic associations may become apparent. Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O2peak response variance, and whether genomic predictors for V̇O2peak response trainability can inform evidence-based clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Id: ACTRN12618000501246, Date Registered: 06/04/2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374601&isReview=true .

中文翻译：

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对间歇和连续运动训练反应的全基因组关联研究：Predict-HIIT 研究

低心肺适能 (V̇O2peak) 与各种原因引起的慢性疾病和死亡率高度相关。虽然健康指南建议进行运动训练以改善 V̇O2peak，但对于相同剂量的运动，V̇O2peak 的反应存在相当大的个体差异。了解遗传因素如何影响 V̇O2peak 训练反应可能会改善锻炼计划的个性化。本研究的目的是确定与运动训练后 V̇O2peak 反应幅度相关的遗传变异。从一项多中心研究 (Predict-HIIT) 中获得了来自 18 种不同干预措施的客观测量 V̇O2peak 的参与者变化。完成了全基因组关联研究（n = 507），并且使用来自与 V̇O2peak 反应的幅度显着相关（P < 1 × 10–5）的单核苷酸多态性（SNP）的等位基因开发了多基因预测评分（PPS）。结果在一项独立的验证研究（n = 39）中进行了测试，并与之前的研究进行了比较。在调整关键协变量（基线 V̇O2peak、个体研究、与性状显着相关的主成分）后，未发现全基因组显着性水平的变异。分位数-分位数图表明研究中存在轻微膨胀。12 个新位点显示出与 V̇O2peak 响应相关的趋势，达到提示意义（P < 1 × 10-5）。在膜相关鸟苷酸激酶、WW 和含有 2 (MAGI2) 基因的 PDZ 域附近发现了最强的关联 (rs6959961, P = 2. 61 × 10–7）。在十倍交叉验证或独立 (n = 39) 验证研究 (P > 0.1) 中，由 12 个主要 SNP 创建的 PPS 无法预测 V̇O2peak 响应。在 Predict-HIIT (P < 1 × 10–4) 和验证研究 (P < × 10–6) 中发现变异的 beta 系数存在显着相关性，表明基因座的一般效应存在，并且具有较高的统计能力，更重要的遗传关联可能会变得明显。需要对当前和以前的发现进行持续研究和验证，以确定遗传学是否确实在 V̇O2peak 反应方差中发挥重要作用，以及 V̇O2peak 反应可训练性的基因组预测因子是否可以为循证临床实践提供信息。试验注册澳大利亚新西兰临床试验注册中心 (ANZCTR)，试验 ID：ACTRN12618000501246，