A Genetic Marker Associated with Shoulder Dislocation

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

Abstract

Shoulder dislocations are common shoulder injuries associated with athletic activity in contact sports, such as football and basketball. Identifying genetic loci associated with shoulder dislocation could shed light on underlying mechanisms for injury and identify predictive genetic markers. In order to identify DNA polymorphisms associated with shoulder dislocation, a genome-wide association screen was performed using publically available data from the Research Program in Genes, Environment and Health including 662 cases of shoulder dislocation and 82,602 controls from the European ancestry group. rs12913965 showed an association with shoulder dislocation at genome-wide significance (p=9.7x10-9; odds ratio=1.6) from the European ancestry group. Individuals carrying one copy of the risk allele (T) at rs12913965 showed a 69% increased risk for shoulder dislocation in our cohort. rs12913965 is located within an intron of TICRR, which encodes TOPBP1 interacting checkpoint and replication regulator involved in the cell cycle. rs12913965 is also associated with changes in expression of ISG20, which encodes an antiviral nuclease induced by interferons. rs12913965 may be the first genetic marker identified for risk of shoulder dislocation. This genetic marker may one day be used to identify athletes with a higher genetic risk for shoulder dislocation. It will be important to replicate this finding in future studies. 
 

Summary Statistics for Shoulder Dislocation. 

Summary statistics for 8046964 SNPs for EUR ancestry group (zipped text file, 203 Mb). 

Summary statistics for 8289991 SNPs for LAT ancestry group (zipped text file, 203 Mb). 

Summary statistics for 7496258 SNPs for EAS ancestry group (zipped text file, 203 Mb). 

CHR: chromosom; SNP: rsid; BP: position in HG18; A1: effect allele; TEST: additive test; NMISS: number of individuals missing SNP data; OR: odds ratio; SE: standard error; L95: lower 95% confidence interval; U95: upper 95% confidence interval; STAT: T statistic; UNADJP: unadjusted p-value; GIF: genomic inflation factor; GCADJP: p-value adjusted for genomic inflation factor

Summary statistics for 7148798 SNPs for fixed effects meta-analysis using EUR and LAT ancestry groups (zipped text file, 215 Mb). 

Summary statistics for 7890511 SNPs for fixed effects meta-analysis using EUR, LAT and EAS ancestry groups (zipped text file, 271 Mb).

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.