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.

背景：与心肌病（CMPs）相关的遗传变异在普通人群中普遍存在。在年轻运动员中，CMPs导致约四分之一的突发性心脏死亡，并在某些特定运动项目中出现进一步的未解释性聚集。因此，大多数CMPs成为竞技体育的禁忌症。我们假设遗传变异可能（出人意料地）在生命早期改善体能表现，而在生命晚期损害心脏功能。方法：通过PubMed的系统检索，探讨与CMPs相关的基因中的遗传变异是否可能与有益的性能表型相关。摘要：在有限的几项研究中（n=6），2860名携带遗传变异的个体/受试者能够在跑步速度（异合子（HET）小鼠的跑步速度约为38米/分钟，n=6 vs. 纯合子（WT）小鼠的跑步速度约为32米/分钟，n=7，P=0.004）和距离（HET小鼠966±169公里 vs. WT小鼠561±144公里，P=0.0035，n=10）方面超越未携带此类变异的个体，在耐力运动员中达到精英运动员水平（n=1672，P=1.43*10^-8），精英运动员的最大摄氧量（绝对差异未提供，n=32，P=0.005），非相关个体的最大摄氧量（n=473，P=0.0025），高训练马拉松跑者的个人记录（HET小鼠2:26:28±0:06:23分钟，n=32 vs. 未携带多态性者2:28:53±0:05:50分钟，n=108，P=0.020），以及接受心脏康复计划的患者的外周肌肉力量收缩（绝对值未提供，n=260）。关键信息：与CMPs相关的遗传变异的有益效应可能在理论上对年轻运动员的选择起到作用，从而解释了此类遗传变异在运动员和普通人群中的普遍性。