Supplementary Material for: Beneficial effects of cardiomyopathy-associated genetic variants on physical performance: a hypothesis-generating scoping review

Background Genetic variants associated with cardiomyopathies (CMPs) are prevalent in the general population. In young athletes, CMPs account for roughly a quarter of sudden cardiac death, with further unexplained clustering in specific sports. Consequently, most CMPs form a contra-indication for competitive sports. We hypothesized that genetic variants might (paradoxically) improve physical performance early in life while impairing cardiac function later in life. Methods Systematic PubMed search to investigate whether genetic variants in genes associated with CMPs could be related to beneficial performance phenotypes. Summary In a limited number of studies (n=6), 2860 individuals/ subjects with genetic variants were able to outperform those without said variants, as measured by running speed (~38 m/min in heterozygous (HET) mice, n=6 vs ~32 m/min in wild type (WT) mice, n=7, P=0.004) and distance (966±169 km HET mice vs 561±144 km WT mice, P=0.0035, n=10), elite athlete status in endurance athletes (n=1672, P=1.43*10-8), maximal oxygen uptake in elite athletes (absolute difference not provided, n=32, P=0.005), maximal oxygen uptake in unrelated individuals (n=473, P=0.0025), personal records in highly trained marathon runners (2:26:28±0:06:23 min HET, n=32 vs. 2:28:53±0:05:50 min without polymorphism, n=108, P=0.020), and peripheral muscle force contraction in patients following a cardiac rehabilitation programme (absolute values not provided, n=260). Key message Beneficial effects in genetic variants associated with CMPs could hypothetically play a role in the selection of young athletes, consequently explaining the prevalence of such genetic variants in athletes and the general population.