ArticleThe Journal of clinical endocrinology and metabolism2025
Cardiorespiratory Fitness, Body Composition, Diabetes, and Longevity: A 2-Sample Mendelian Randomization Study.
Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed.
- Aerobic Fitness and Health-Related Phenotypes: A Two-Stage Phenome-Wide Mendelian Randomization Study.Medicine and science in sports and exercise · 2026Article
- Evaluation of Genetics in the Association Between Cardiorespiratory Fitness and Health: Insights from a Genome-Wide Polygenic Score for Cardiorespiratory Fitness in the FinnGen and HUNT cohorts.Scandinavian journal of medicine & science in sports · 2026Article
- Monitoring muscle oxygen saturation during forest trail hiking: a prospective open-label quasi-experimental study with facility-based allocation examining physiological and immunological responses in older adults.Scientific reports · 2026Article
- A polygenetic rat model of divergent aerobic capacity reveals a liver-brain interaction impacting Alzheimer's disease-like phenotypes.The Journal of physiology · 2026Article
- Cardiorespiratory fitness and type 2 diabetes risk: A prospective cohort study with mediation analysis of biological aging in the UK Biobank.Diabetes, obesity & metabolism · 2026Article
- Polygenic prediction of cardiorespiratory fitness in the Trøndelag health study (HUNT).Scientific reports · 2025Article
- Cardiorespiratory Fitness, Body Composition, Diabetes, and Longevity: A 2-Sample Mendelian Randomization Study.The Journal of clinical endocrinology and metabolism · 2025Article
- Cardiorespiratory fitness in adolescence and risk of type 2 diabetes in late adulthood in one million Swedish men: nationwide sibling controlled cohort study.BMJ medicine · 2025Article
- Cardiorespiratory Fitness in Adolescence and Risk of Type 2 Diabetes in Late Adulthood: A Nationwide Sibling-Controlled Cohort Study.medRxiv : the preprint server for health sciences · 2024Article
- Maximal Oxygen Consumption Is Negatively Associated with Fat Mass in Facioscapulohumeral Dystrophy.International journal of environmental research and public health · 2024Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
contextCardiorespiratory fitness, commonly assessed as maximal volume of oxygen consumption (VO2max), has emerged as an important predictor of morbidity and mortality.
objectiveWe investigated the causality and directionality of the associations of VO2max with body composition, physical activity, diabetes, performance enhancers, and longevity.
methodsUsing publicly available summary statistics from the largest genome-wide association studies publicly available, we conducted a bidirectional 2-sample Mendelian randomization (MR) study. Bidirectional MR tested directionality, and estimated the total causal effects, whereas multivariable MR (MVMR) estimated independent causal effects. Cardiorespiratory fitness (VO2max) was estimated from a submaximal cycle ramp test (N ≈ 70 000) and scaled to total body weight, and in additional analyses to fat-free mass (mL/min/kg).
resultsGenetically predicted higher (per 1 SD increase) body fat percentage was associated with lower VO2max (β = -0.36; 95% CI: -0.40, -0.32, P = 6 × 10-77). Meanwhile, genetically predicted higher appendicular lean mass (β = 0.10; 95% CI: 0.08 to 0.13), physical activity (β = 0.29; 95% CI: 0.07 to 0.52), and performance enhancers (fasting insulin, hematocrit, and free testosterone in men) were all positively associated with VO2max (all P < .01). Genetic predisposition to diabetes had no effect on VO2max. MVMR showed independent causal effects of body fat percentage, appendicular lean mass, physical activity, and hematocrit on VO2max, as well as of body fat percentage and type 2 diabetes (T2D) on longevity. Genetically predicted VO2max showed no associations.
conclusionCardiorespiratory fitness can be improved by favorable body composition, physical activity, and performance enhancers. Despite being a strong predictor of mortality, VO2max is not causally associated with T2D or longevity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.