Two Genetic Loci Associated with Ankle Injury

Stuart K. Kim, John P. Kleimeyer, Marwa A. Ahmed, Andrew L. Avins, Michael Fredericson, Jason L. Dragoo and John P. A. Ioannidis

PLoS ONE 12(9): e0185355.


Ankle sprains, ankle strains and ankle joint derangements are common injuries, especially for athletes involved in an indoor court or jumping sport. Identifying genetic loci associated with these ankle injuries could shed light on its etiology. A genome-wide association screen was performed using publically available data from the Research Program in Genes, Environment and Health (RPGEH) including 1,694 cases of ankle injury and 97,646 controls. An indel (chr21:47156779:D on chromosome 21) that lies close to a collagen gene, COL18A1, showed an association with ankle injury at genome-wide significance (p=3.8x10-8; OR=1.99; 95% CI=1.75-2.23). A second DNA variant (rs13286037 on chromosome 9) that lies within an intron of the transcription factor gene NFIB showed an association that was nearly genome-wide significant (p=5.1x10-8; OR=1.63; 95% CI=1.46-1.80). The ACTN3 R577X mutation was previously reported to show an association with acute ankle sprains, but did not show an association in this cohort. This study is the first genome-wide screen for ankle injury that yields insights regarding the genetic etiology of ankle injuries and provides DNA markers with the potential to inform athletes about their genetic risk for ankle injury.