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A Genome Wide Association Study For Shoulder Impingement and Rotator Cuff Disease.

Abstract：

BACKGROUND:The purpose of the study was to identify genetic variants associated with rotator cuff disease by performing a genome-wide association study (GWAS) for shoulder impingement utilizing the UK Biobank (UKB) cohort, and then combining the GWAS data with a prior GWAS for rotator cuff tears. The loci identified by the GWAS and meta-analysis were examined for changes in expression following rotator cuff tearing using RNA sequencing. METHODS:GWA Study: A GWAS was performed using data from UKB with 3,864 cases of shoulder impingement. The summary statistics from shoulder impingement and a prior study on rotator cuff tears were combined in a meta-analysis. Also, the previous association of two single nucleotide polymorphisms (SNPs) with shoulder impingement from a published GWAS using the UKB were tested. RNA SEQUENCING ANALYSES:Rotator cuff tendon biopsies were obtained from 24 patients with full-thickness rotator cuff tears that underwent arthroscopic rotator cuff repair (cases) and 9 patients that underwent open reduction internal fixation for a proximal humeral fracture (controls). Total RNA was extracted and differential gene expression was measured by RNA sequencing for genes with variants associated with rotator cuff tearing. RESULTS:The shoulder impingement GWAS identified four new loci: LOC100506457, LSP1P3, LOC100506207 and MIS18BP1/LINC00871. Combining data with a prior GWAS for rotator cuff tears in a meta-analysis resulted in the identification of an additional seven loci: SLC39A8/UBE2D3, C5orf63, ASTN2, STK24, FRMPD4, ACOT9/SAT1 and LINC00890/ALG13. Many of the identified loci have known biological functions or prior associations with diseases suggesting possible biological pathways leading to rotator cuff disease. RNA sequencing experiments shows that expression of STK24 increases whereas expression of SAT1 and UBE2D3 decreases following rotator cuff tearing. Two SNPs previously reported to show an association with shoulder impingement from a prior UKB GWAS were not validated in our study. CONCLUSION:This is the first GWAS for shoulder impingement in which new data from UKB enabled the identification of four loci showing a genetic association. A meta-analysis with a prior GWAS for rotator cuff tearing identified an additional seven loci. The known biological roles of many of the 11 loci suggest plausible biological mechanisms underlying the etiology of rotator cuff disease. The risk alleles from each of the genetic loci can be used to assess the risk for rotator cuff disease in individual patients, enabling preventative or restorative actions via personalized medicine. LEVEL OF EVIDENCE:Basic Science Study; Molecular Biology.

journal_name

J Shoulder Elbow Surg

journal_title

Journal of shoulder and elbow surgery

authors

Kim SK,Nguyen C,Jones KB,Tashjian RZ

doi

10.1016/j.jse.2020.11.025

subject

Has Abstract

pub_date

2021-01-19 00:00:00

eissn

1058-2746

issn

1532-6500

pii

S1058-2746(21)00015-X

pub_type

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A Genome Wide Association Study For Shoulder Impingement and Rotator Cuff Disease.