Genetic Epidemiology of Rotator Cuff Tears: The cuffGEN Study


Rotator cuff tear is one of the most common reasons to seek musculoskeletal care, and cuff repair is one of the fastest growing ambulatory surgery procedures. However, the etiology of cuff tears, reasons for variability treatment success, and causes of FI are poorly understood. A large-scale genome-wide association studies (GWAS) using imaging-verified rotator cuff tear cases and controls can address limitations in rigor of prior research and assess the genetic basis of FI and functional outcomes of cuff tear treatments. Primary Objective: To conduct a case-control GWAS of imaging-verified symptomatic rotator cuff tear in approximately 3000-6000 individuals and replicate findings in an independent set of 3000-6000 or more imaging-verified individuals to identify common variants in several genetic loci that increase risk for rotator cuff tears. Hypothesis: Common variants in several genetic loci increase risk for rotator cuff tears. Secondary Objectives: 1. To perform an imputed transcriptome-wide association study (TWAS) to identify and prioritize gene targets associated with rotator cuff tear by integrating GWAS summary statistics and gene-expression weights from muscle and adipose tissue available in the GTEx project. Hypothesis: Genetically predicted gene expression of multiple genes in muscle and adipose tissue are associated with rotator cuff tear. 2. To identify if single nucleotide polymorphisms (SNPs) associated with rotator cuff tear and their genetic risk score (GRS) predict improved pain and function as measured by American Shoulder and Elbow Surgeons Standardized Form (ASES) and other outcome measures. Hypothesis: Select SNPs and GRS predict ASES outcome. 3. To identify genetic variants associated with Fatty Infiltration (FI) in patients with cuff tears in a two stage GWAS of imaged rotator cuffs and to prioritize gene targets through an imputed-TWAS in muscle and adipose tissue. Hypothesis: Multiple genetic variants are associated with FI and some exert their influence by altering gene expression in the muscle and adipose tissue.

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Other
  • Study Primary Completion Date: December 31, 2026


  • Other: NA (not an interventional study)
    • (not an interventional study)

Arms, Groups and Cohorts

  • Case
    • Patients with MRI confirmed rotator cuff tears
  • Control
    • Patients without rotator cuff tears

Clinical Trial Outcome Measures

Primary Measures

  • Genome wide association meta-analysis of cases and controls
    • Time Frame: 10 years
    • Discovery of targeted variants in MRI verified cases and controls

Participating in This Clinical Trial

Inclusion Criteria

  • Aged ≥40 years to < 85 years – Confirmed diagnosis of partial or full-thickness cuff tear on MRI (Cases) OR absence of rotator cuff tear on shoulder MRI (Controls) – Ability and willingness to provide informed consent – Ability to complete questionnaires in English (to maintain scientific integrity since standardized questionnaires are extensively validated in English) Exclusion Criteria:

  • Acute rotator cuff tear caused by a severe trauma

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: 85 Years

Investigator Details

  • Lead Sponsor
    • University of Texas Southwestern Medical Center
  • Collaborator
    • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  • Provider of Information About this Clinical Study
    • Principal Investigator: Nitin Jain, Professor of Physical Medicine & Rehabilitation, Orthopaedics, and Population & Data Sciences – University of Texas Southwestern Medical Center
  • Overall Official(s)
    • Nitin Jain, MD, Principal Investigator, UTexasSouthwester
  • Overall Contact(s)
    • Nitin Jain, MD, 214-645-0053,

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