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

Journal of Biomedical Science

Erin J. Howden¹  Dorthe Stensvold²  Anja Bye³  Jeff S. Coombes⁴  Camilla J. Williams⁴  Shelley E. Keating⁴  Robert G. Fassett⁴  Jenna L. Taylor⁴  Trishan Gajanand⁴  Emily R. Cox⁴  Ulrik Wisloff⁵  Ilaria Croci⁶  Joyce S. Ramos⁷  Emeline M. Van Craenenbroeck⁸  Paul Beckers⁸  Véronique A. Cornelissen⁹  Luciana Torquati^1,10  Kevin J. Ashton^1,11  Nicholas Harvey^1,12  Matthew A. Brown^1,13  Macsue Jacques^1,14  Nir Eynon^1,14  Ioannis Papadimitriou^1,14  Xu Yan^1,15  David J. Bishop^1,16  Satyam Sarma^1,17  Christopher M. Hearon^1,17  Sylvan L. J. E. Janssen^1,18  Rodney A. Lea^1,19  Lyn R. Griffiths^1,19  Larisa M. Haupt^1,19  Monique E. Francois^2,20  Jonathan P. Little^2,20  Jacob T. Bonafiglia^2,21  Brendon J. Gurd^2,21  Zhixiu Li^2,22 

[1] Baker Heart and Diabetes Institute, Melbourne, VIC, Australia;Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway;Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway;Department of Cardiology, St. Olavs Hospital, Trondheim, Norway;Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, University of Queensland, St. Lucia, Brisbane, QLD, Australia;Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, University of Queensland, St. Lucia, Brisbane, QLD, Australia;Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway;Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, University of Queensland, St. Lucia, Brisbane, QLD, Australia;Cardiac Exercise Research Group (CERG), Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway;Department of Sport, Movement and Health, University of Basel, Basel, Switzerland;Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, University of Queensland, St. Lucia, Brisbane, QLD, Australia;Caring Futures Institute, SHAPE Research Centre, Exercise Science and Clinical Exercise Physiology, College of Nursing and Health Sciences, Flinders University, Adelaide, SA, Australia;Department of Cardiology, Antwerp University Hospital, Antwerp, Belgium;Department of Rehabilitation Sciences – Research Group for Rehabilitation in Internal Disorders, Catholic University of Leuven, Leuven, Belgium;Department of Sport and Health Sciences, University of Exeter, Exeter, UK;Faculty of Health Sciences and Medicine, Bond University, Robina, QLD, Australia;Faculty of Health Sciences and Medicine, Bond University, Robina, QLD, Australia;Queensland University of Technology (QUT), Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Kelvin Grove, Brisbane, QLD, Australia;Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London, UK;Institute for Health and Sport (iHeS), Victoria University, Melbourne, VIC, Australia;Institute for Health and Sport (iHeS), Victoria University, Melbourne, VIC, Australia;Australia Institute for Musculoskeletal Sciences (AIMSS), Melbourne, VIC, Australia;Institute for Health and Sport (iHeS), Victoria University, Melbourne, VIC, Australia;School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia;Internal Medicine, Institute for Exercise and Environmental Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA;Internal Medicine, Institute for Exercise and Environmental Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA;Department of Physiology, Radboud University Medical Center, Nijmegen, Netherlands;Queensland University of Technology (QUT), Centre for Genomics and Personalised Health, Genomics Research Centre, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Kelvin Grove, Brisbane, QLD, Australia;School of Health and Exercise Sciences, University of British Columbia, Kelowna, BC, Canada;School of Kinesiology and Health Studies, Queen’s University, Kingston, ON, Canada;Translational Genomics Group, Institute of Health and Biomedical Innovation, Woolloongabba, Brisbane, QLD, Australia;

关键词: Genetics;    V̇Opeak training response;    Individual variability;    GWAS;    Polygenic predictor score;   

DOI  :  10.1186/s12929-021-00733-7

来源: Springer

【 摘 要 】

BackgroundLow 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.MethodsParticipant 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.ResultsNo 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.ConclusionsOngoing 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.

【 授权许可】

CC BY