Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study.

Background: Low cardiorespiratory fitness (V̇O _2peak ) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O _2peak , there is considerable inter-individual variability in the V̇O _2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O _2peak 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 V̇O ₂ peak response following exercise training.
Methods: Participant change in objectively measured V̇O ₂ peak 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 V̇O ₂ peak response. Findings were tested in an independent validation study (n = 39) and compared to previous research.
Results: No variants at the genome-wide significance level were found after adjusting for key covariates (baseline V̇O ₂ peak _, 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 V̇O ₂ peak 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 V̇O ₂ peak 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.
Conclusions: Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O ₂ peak response variance, and whether genomic predictors for V̇O ₂ peak 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 .