The APOE ε4 allele is a candidate genetic marker for risk and severity of mild traumatic brain injury (mTBI) including sport-related concussion. ε4 allele carriers experience reduced motor rehabilitation outcomes, poorer neurocognitive outcomes, increased cognitive impairments, amnesia and memory defects following mTBI. Concussion injury (mTBI) rates in elite rugby players are substantial and, consequently, elevated risk and severity of mTBI due to carriage of the ε4 risk allele may be detrimental to both the short-term and long-term health of elite players and reduce their likelihood of career success. Therefore, we investigated APOE ε2/ε3/ε4 of athletes at the elite level of competitive rugby. Genomic DNA was collected from 1006 Caucasian participants, comprising 523 elite rugby athletes and 483 non-athlete controls (RugbyGene study). All samples were genotyped for the APOE ε2/ε3/ε4 variants (rs429358 and rs7412) using real-time PCR. No genotype differences (P > 0.05) were identified between controls (ε4/ε4 = 2.3%) and either rugby union (ε4/ε4 = 3.7%) or rugby league (ε4/ε4 = 1.3%) athletes. Similarly, when the presence of the ε4 allele (ε4+) was compared to non-carriers, no allelic differences were observed between controls (ε4+ = 28%) and either rugby union (ε4+ = 29%) or rugby league (ε4+ = 33%). Rugby union athletes with international competitive experience showed an underrepresentation of the ε4/ε4 genotype compared to those without international experience (2.6% versus 4.7%, P = 0.01), but exhibited a similar frequency to controls (2.3%). These results suggest that APOE ε4 plays little or no role in the likelihood of a rugby athlete achieving elite competitive status. However, our data suggest that ~30% of rugby athletes could be at greater risk of poor recovery from concussion due to carriage of the ε4 APOE allele and this warrants research to establish if previously identified APOE ε4-mTBI associated outcomes exist in elite rugby.

Two common single nucleotide polymorphisms within the COL5A1 gene (SNPs; rs12722 C/T and rs3196378 C/A) have previously been associated with tendon and ligament pathologies. Given the high incidence of tendon and ligament injuries in elite rugby athletes, we hypothesised that both SNPs would be associated with career success. In 1105 participants (RugbyGene project), comprising 460 elite rugby union (RU), 88 elite rugby league athletes and 565 non-athlete controls, DNA was collected and genotyped for the COL5A1 rs12722 and rs3196378 variants using real-time PCR. For rs12722, the injury-protective CC genotype and C allele were more common in all athletes (21% and 47%, respectively) and RU athletes (22% and 48%) than in controls (16% and 41%, P ≤ 0.01). For rs3196378, the CC genotype and C allele were overrepresented in all athletes (23% and 48%) and RU athletes (24% and 49%) compared to controls (16% and 41%, P ≤ 0.02). The CC genotype in particular was overrepresented in the back and centres (24%) compared to controls, with more than twice the odds (OR = 2.25, P = 0.006) of possessing the injury-protective CC genotype. Furthermore, when considering both SNPs simultaneously, the CC–CC SNP-SNP combination and C–C inferred allele combination were higher in all the athlete groups (≥ 18% and ≥ 32%) compared to controls (13% and 27%; P = 0.01). However, no genotype differences were identified for either SNP when RU playing positions were compared directly with each other. It appears that the C alleles, CC genotypes and resulting combinations of both rs12722 and rs3196378 are beneficial for rugby athletes to achieve elite status and carriage of these variants may impart an inherited resistance against soft tissue injury, despite exposure to the high-risk environment of elite rugby. These data have implications for the management of inter-individual differences in injury risk amongst elite athletes.