Identification of Three Loci Associated with Achilles Tendon Injury Risk from a Genome-wide Association Study

To screen the entire genome for genetic markers associated with risk for Achilles tendon injury. A genome-wide-association (GWA) analysis was performed utilizing data from the Kaiser Permanente Research Board (KPRB) and the United Kingdom (UK) Biobank. Achilles tendon injury cases were identified based on electronic health records from the KPRB databank and the UK Biobank from individuals of European ancestry. Genome-wide association analyses from both cohorts were tested for Achilles tendon injury using a logistic regression model adjusting for sex, height, weight and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). Previously identified genes within the literature were also tested for association with Achilles tendon injury. There was a total of 12,354 cases of Achilles tendon injury and 483,080 controls within the two combined cohorts, with 67 SNPs in three chromosomal loci demonstrating a genome-wide significant association with Achilles tendon injury. The first locus contains a single SNP (rs183364169) near the CDCP1 and TMEM158 genes on chromosome 3. The second locus contains 65 SNPs in three independently segregating sets near the MPP7 gene on chromosome 10. The last locus contains a single SNP (rs4454832) near the SOX21 and GPR180 genes on chromosome 13. The current data was used to test 14 candidate genes previously reported to show an association with Achilles tendon injury, but none showed a significant association (all p > 0.05). Three loci were identified as potential risk factors for Achilles tendon injury and deserve further validation and investigation of molecular mechanisms.