Abstract
BACKGROUND: The etiology of adhesive capsulitis involves inflammation, thickening and fibrosis of the shoulder capsule. The underlying genetic factors are poorly understood. The purpose of this study was to identify genetic variants associated with adhesive capsulitis utilizing the UK Biobank (UKB) cohort and compare them with variants associated with Dupuytren's disease investigating a common etiology between the two fibrotic disorders.METHODS: Genome-Wide Association (GWA) Study: A GWAS was performed using data from UKB with 10,773 cases of adhesive capsulitis. A second GWAS was performed with 8,891 cases of Dupuytren's disease. Comparison of adhesive capsulitis and Dupuytren's disease: A comparison of association statistics was performed between diseases using the data from both GWAS. Validation of SNPs Previously Reported to Show an Association with Dupuytren's Disease or Adhesive Capsulitis: SNPs previously reported from candidate gene studies for adhesive capsulitis and Dupuytren's disease were tested for association with adhesive capsulitis and Dupuytren's disease using the summary statistics from their respective GWAS.RESULTS: The UKB GWAS for adhesive capsulitis identified six loci that reached genome-wide statistical significance: a cluster of 11 closely-linked SNPs on chromosome 1; a single SNP on chromosome 2; a single SNP on chromosome 14; two closely-linked SNPs on chromosome 21; 33 closely-linked SNPs on chromosome 22; and three closely-linked SNPs on the X chromosome. These SNPs were associated with 8 different genes including TSPAN2/NGF, SATB2, MRPL52/MMP14, ERG, WNT7B and FGF13. A GWAS for Dupuytren's disease was performed and a comparison to the adhesive capsulitis GWAS showed 13 loci significantly associated with both phenotypes. A validation attempt of six previously reported SNPs associated with adhesive capsulitis using UKB summary statistics was unable to confirm any of the previously reported SNPs (all p>0.19). All 23 previously reported SNPs associated with Dupuytren's disease were confirmed using the UKB summary statistics (p < 2.1 x 10-3) CONCLUSION: This GWAS investigating adhesive capsulitis has identified six novel loci involving 8 different genes to be associated with adhesive capsulitis. A GWAS investigating Dupuytren's disease was performed and compared to the adhesive capsulitis GWAS and 13 common loci were identified between the two disorders with genes involved in pathologic fibrosis. We were unable to validate the SNPs in candidate genes previously reported to be associated with adhesive capsulitis although we were able to confirm all previously reported SNPs associated with Dupuytren's disease. The strong genetic overlap between the adhesive capsulitis and Dupuyten's disease loci suggests a similar etiology between the two diseases.
View details for DOI 10.1016/j.jse.2022.07.005
View details for PubMedID 35987430