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Bone mineral density (BMD) is a multi-factorial phenotype determined by factors such as physical activity, diet and a sizeable genetic component. Athletic populations tend to possess higher BMD than non-athletes due to a larger volume of exercise completed. Despite this, some endurance runners can possess low BMD and/or suffer stress fractures, which can have negative impacts on their health and performance. Therefore, we hypothesised that elite endurance runners would possess a genotype associated with enhanced BMD and a reduced risk of injury, resulting in less training interruption and greater potential success. The study compared the genotype and allele frequencies of 5 genetic variants associated with BMD (LRP5 rs3736228, TNFRSF11B rs4355801, VDR rs2228570, WNT16 rs3801387, AXIN1 rs9921222) in elite (men <2 hour 30 min, n=110; women <3 hour 00 min, n=98) and sub-elite (men 2 hour 30 min – 2 hour 45 min, n=181; women 3 hour 00 min – 3 hour 15 min, n=67) marathon runners with those of a non-athlete control population (n=474). We also investigated whether marathon personal best time was associated with a more ‘advantageous’ BMD genotype. Congruent with our hypothesis, the ‘risk’ T allele for the AXIN1 rs9921222 polymorphism was 5% more frequent in the control group than in sub-elites (p=0.030, χ2=4.69) but no further differences were observed for this variant (p≥0.083, χ2 ≤4.98). WNT16 rs3801387 genotype frequency differed between athletes and controls (p=0.002, χ2=12.02) and elites vs controls (p=0.008, χ2=9.72), as did allele frequency. However, contrary to our hypothesis, it was the ‘risk’ A allele that was ~5% more frequent in athletes than controls. Similarly, when combining data from all 5 variants, the athletes had a lower Total Genotype Score than controls (53.6 vs 65.7; p≤0.001), again suggesting greater genetic susceptibility to bone injury in athletes. Personal best times were not associated with genotype in any comparison. These results suggest that high-level endurance runners do not benefit from genetic resistance to bone injury and a resulting ability to sustain large training volumes, contradicting our hypothesis. High-level endurance runners appear to be at a higher risk of bone injury from a genetic perspective, for as yet unexplained reasons, although large inter-individual differences in genetic risk exist.