Anja Bye1, Marie Klevjer2, Einar Ryeng3, Gustavo Jose Justo da Silva4, Jose Bianco Nascimento Moreira2, Dorthe Stensvold5, Ulrik Wisløff6. 1. Cardiac Exercise Research Group (CERG) at Dept. of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Cardiology, St. Olavs Hospital, Trondheim, Norway. Electronic address: Anja.Bye@ntnu.no. 2. Cardiac Exercise Research Group (CERG) at Dept. of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Cardiology, St. Olavs Hospital, Trondheim, Norway. 3. Genomics Core Facility (GCF), Norwegian University of Science and Technology (NTNU), Trondheim, Norway. 4. Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway. 5. Cardiac Exercise Research Group (CERG) at Dept. of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. 6. Cardiac Exercise Research Group (CERG) at Dept. of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; School of Human Movement & Nutrition Sciences, University of Queensland, Brisbane, Australia.
Abstract
INTRODUCTION: Low maximal oxygen uptake (VO2max) is a strong and independent risk factor for all-cause and cardiovascular disease (CVD) mortality. For other CVD risk factors, numerous genetic association studies have been performed, revealing promising risk markers and new therapeutic targets. However, large genomic association studies on VO2max are still lacking, despite the fact that VO2max has a large genetic component. METHODS: We performed a genetic association study on 123.545 single-nucleotide polymorphisms (SNPs) and directly measured VO2max in 3470 individuals (exploration cohort). Candidate SNPs from the exploration cohort were analyzed in a validation cohort of 718 individuals, in addition to 7 wild-card SNPs. Sub-analyses were performed for each gender. Validated SNPs were used to create a genetic score for VO2max. In silico analyses and genotype-phenotype databases were used to predict physiological function of the SNPs. RESULTS: In the exploration cohort, 41 SNPs were associated with VO2max (p < 5.0 ∗ 10-4). Six of the candidate SNPs were associated with VO2max also in the validation cohort, in addition to three wild-card SNPs (p < 0.05, in men, women or both). The cumulative number of high-VO2max-SNPs correlated negatively with CVD risk factors, e.g. waist-circumference, visceral fat, fat %, cholesterol levels and BMI. In silico analysis indicated that several of the VO2max-SNPs influence gene expression in adipose tissue, skeletal muscle and heart. CONCLUSION: We discovered and validated new SNPs associated with VO2max and proposed possible links between VO2max and CVD. Studies combining several large cohorts with directly measured VO2max are needed to identify more SNPs associated with this phenotype.
INTRODUCTION: Low maximal oxygen uptake (VO2max) is a strong and independent risk factor for all-cause and cardiovascular disease (CVD) mortality. For other CVD risk factors, numerous genetic association studies have been performed, revealing promising risk markers and new therapeutic targets. However, large genomic association studies on VO2max are still lacking, despite the fact that VO2max has a large genetic component. METHODS: We performed a genetic association study on 123.545 single-nucleotide polymorphisms (SNPs) and directly measured VO2max in 3470 individuals (exploration cohort). Candidate SNPs from the exploration cohort were analyzed in a validation cohort of 718 individuals, in addition to 7 wild-card SNPs. Sub-analyses were performed for each gender. Validated SNPs were used to create a genetic score for VO2max. In silico analyses and genotype-phenotype databases were used to predict physiological function of the SNPs. RESULTS: In the exploration cohort, 41 SNPs were associated with VO2max (p < 5.0 ∗ 10-4). Six of the candidate SNPs were associated with VO2max also in the validation cohort, in addition to three wild-card SNPs (p < 0.05, in men, women or both). The cumulative number of high-VO2max-SNPs correlated negatively with CVD risk factors, e.g. waist-circumference, visceral fat, fat %, cholesterol levels and BMI. In silico analysis indicated that several of the VO2max-SNPs influence gene expression in adipose tissue, skeletal muscle and heart. CONCLUSION: We discovered and validated new SNPs associated with VO2max and proposed possible links between VO2max and CVD. Studies combining several large cohorts with directly measured VO2max are needed to identify more SNPs associated with this phenotype.
Authors: Giorgia Benegiamo; Maroun Bou Sleiman; Martin Wohlwend; Sandra Rodríguez-López; Ludger J E Goeminne; Pirkka-Pekka Laurila; Marie Klevjer; Minna K Salonen; Jari Lahti; Pooja Jha; Sara Cogliati; José Antonio Enriquez; Ben M Brumpton; Anja Bye; Johan G Eriksson; Johan Auwerx Journal: Nat Metab Date: 2022-10-17
Authors: Angelo Sabag; Shelley E Keating; Kimberley L Way; Rachelle N Sultana; Sean M Lanting; Stephen M Twigg; Nathan A Johnson Journal: BMC Sports Sci Med Rehabil Date: 2021-04-16