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Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study Williams, Camilla J; Li, Zhixiu; Harvey, Nicholas; Lea, Rodney A; Gurd, Brendon J; Bonafiglia, Jacob T; Papadimitriou, Ioannis; Jacques, Macsue; Croci, Ilaria; Stensvold, Dorthe; Wisloff, Ulrik; Taylor, Jenna L; Gajanand, Trishan; Cox, Emily R; Ramos, Joyce S; Fassett, Robert G; Little, Jonathan P.; Francois, Monique E.; Hearon, Christopher M; Sarma, Satyam; Janssen, Sylvan L J E; Van Craenenbroeck, Emeline M; Beckers, Paul; Cornelissen, Véronique A; Howden, Erin J; Keating, Shelley E; Yan, Xu; Bishop, David J; Bye, Anja; Haupt, Larisa M; Griffiths, Lyn R; Ashton, Kevin J; Brown, Matthew A; Torquati, Luciana; Eynon, Nir; Coombes, Jeff S
Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: 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 .
Item Metadata
Title |
Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study
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Creator |
Williams, Camilla J; Li, Zhixiu; Harvey, Nicholas; Lea, Rodney A; Gurd, Brendon J; Bonafiglia, Jacob T; Papadimitriou, Ioannis; Jacques, Macsue; Croci, Ilaria; Stensvold, Dorthe; Wisloff, Ulrik; Taylor, Jenna L; Gajanand, Trishan; Cox, Emily R; Ramos, Joyce S; Fassett, Robert G; Little, Jonathan P.; Francois, Monique E.; Hearon, Christopher M; Sarma, Satyam; Janssen, Sylvan L J E; Van Craenenbroeck, Emeline M; Beckers, Paul; Cornelissen, Véronique A; Howden, Erin J; Keating, Shelley E; Yan, Xu; Bishop, David J; Bye, Anja; Haupt, Larisa M; Griffiths, Lyn R; Ashton, Kevin J; Brown, Matthew A; Torquati, Luciana; Eynon, Nir; Coombes, Jeff S
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Publisher |
BioMed Central
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Date Issued |
2021-05-13
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Description |
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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
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Subject | |
Genre | |
Type | |
Language |
eng
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Date Available |
2021-05-13
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution 4.0 International (CC BY 4.0)
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DOI |
10.14288/1.0397480
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URI | |
Affiliation | |
Citation |
Journal of Biomedical Science. 2021 May 13;28(1):37
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Publisher DOI |
10.1186/s12929-021-00733-7
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Peer Review Status |
Reviewed
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Scholarly Level |
Faculty
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Copyright Holder |
The Author(s)
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Rights URI | |
Aggregated Source Repository |
DSpace
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Item Citations and Data
Rights
Attribution 4.0 International (CC BY 4.0)