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

Abstract

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.
 

Summary Statistics for ankle injury. 

Summary statistics for 8183964 SNPs for fixed effects meta-analysis using EUR, LAT and EAS ancestry groups (zipped text file, 280 Mb).

CHR: chromosom; BP: position in HG18; SNP: rsid; A1: effect allele; A2: other allele; N: number of ancestry groups; P: p-value from fixed effects meta_analysis; P(R): p-value from random effects meta_analysis; OR: allelic fixed effects odds ratio; OR(R): allelic random effects odds ratio; Q: Cochran's Q value; I: I^2 for heterogeneity; WEIGHTED_Z: weighted Z-score, as computed by METAL; P(WZ): p-value for weighted Z-score; F0: odds ratio for EUR; F1: odds ratio for LAT; F3: odds ratio for EAS.