INTRODUCTION: Aim of this systematic review and meta-analysis was to identify the genetic variants of (inter)national competing runners and cyclists compared to controls. METHODS: The Medline and Embase databases were searched until 15 November 2021. Eligible articles included genetic epidemiological studies published in English. Runners and cyclists competing at (inter)national level and sedentary controls were eligible for inclusion. Pooled odds ratios based on genotype frequency with corresponding 95% confidence intervals (95%CI) were calculated using random effects models. Heterogeneity was addressed by Q-statistics and I2. Sources of heterogeneity were examined by meta-regression and risk of bias was assessed with the Clark Baudouin scale. RESULTS: This systematic review comprised of 43 studies including a total of 3815 athletes and 10630 controls in the pooled analysis. Of the 43 identified genetic variants, 13 were replicated in independent studies. Significant associations were found for five polymorphisms. Pooled odds ratio [95%CI] favoring athletes compared to controls was 1.51 [1.22-1.88] for ACE (rs1799752), 1.66 [1.26-2.19] for ACTN3 (rs1815739), 1.75 [1.34-2.29] for PPARGC1A (rs8192678), 2.23 [1.42-3.51] for AMPD1 (rs17602729), and 2.85 [1.27; 6.39] for HFE (rs1799945). Risk of bias was low in 25 (58%) and unclear in 18 (42%) articles. Heterogeneity of the pooled results was low (0-19.1%) except for HFE (71%), GNB3 (80.1%) and NOS3 (76%). CONCLUSION: (Inter)national competing runners and cyclists have a higher probability to carry specific genetic variants compared to controls.
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