Genetics of long-distance runners and road cyclists - a systematic review with meta-analysis

The aim of this systematic review and meta-analysis was to identify the genetic variants of (inter)national competing long-distance runners and road cyclists compared to controls. The Medline and Embase databases were searched until 15 November 2021. Eligible articles included genetic epidemiological studies published in English. A homogenous group of endurance athletes competing at (inter)national level and sedentary controls were included. 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. This systematic review comprised of 43 studies including a total of 3938 athletes and 10752 controls in the pooled analysis. Of the 42 identified genetic variants, 13 were investigated in independent studies. Significant associations were found for five polymorphisms. Pooled odds ratio [95%CI] favoring athletes compared to controls was 1.42 [1.12-1.81] for ACE II (I/D), 1.66 [1.26-2.19] for ACTN3 TT (rs1815739), 1.75 [1.34-2.29] for PPARGC1A GG (rs8192678), 2.23 [1.42-3.51] for AMPD1 CC (rs17602729), and 2.85 [1.27-6.39] for HFE GG+CG (rs1799945). Risk of bias was low in 25 (58%) and unclear in 18 (42%) articles. Heterogeneity of the results was low (0-20%) except for HFE (71%), GNB3 (80%), and NOS3 (76%). (Inter)national competing runners and cyclists have a higher probability to carry specific genetic variants compared to controls. This study confirms that (inter)national competing endurance athletes constitute a unique genetic make-up, which likely contributes to their performance level.