Kim, Stuart K.Kleimeyer, John P.Ahmed, MarwaAvins, Andrew L.Fredericson, MichaelDragoo, Jason L.Ioannidis, John P. A.2017-12-062017Kim, Stuart K., John P. Kleimeyer, Marwa A. Ahmed, Andrew L. Avins, Michael Fredericson, Jason L. Dragoo, and John P. A. Ioannidis. 2017. “Two genetic loci associated with ankle injury.” PLoS ONE 12 (9): e0185355. doi:10.1371/journal.pone.0185355. http://dx.doi.org/10.1371/journal.pone.0185355.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492278Ankle injuries, including sprains, strains and other joint derangements and instability, are common, especially for athletes involved in indoor court or jumping sports. Identifying genetic loci associated with these ankle injuries could shed light on their etiologies. A genome-wide association screen was performed using publicly 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) 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.en-USBiology and Life SciencesAnatomyMusculoskeletal SystemLimbs (Anatomy)LegsAnklesMedicine and Health SciencesBiological TissueConnective TissueLigamentsCritical Care and Emergency MedicineTrauma MedicineTraumatic InjuryMusculoskeletal InjuryComputational BiologyGenome AnalysisGenome-Wide Association StudiesGeneticsGenomicsHuman GeneticsGenetic LociMathematical and Statistical TechniquesStatistical MethodsMeta-AnalysisPhysical SciencesMathematicsStatistics (Mathematics)Molecular GeneticsMolecular BiologyBiology and life sciencesGene expressionDNA transcriptionJournal Article2017-12-0610.1371/journal.pone.0185355