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Genetic Epidemiology of Rotator Cuff Tears: The cuffGEN Study

Who can join

Ages 40 to 85 · All sexes

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

About the 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.

What is being tested

• NA (not an interventional study) (other)

Sponsor: University of Michigan · Participants: 3,500 · Started: Mar 4, 2021

Contact the study team

• Nitin Jain, MD · Phone: 734-936-8178
• Sravanthi Kaza, MS · Phone: 814-323-4754

Official record on ClinicalTrials.gov — NCT04831164

Locations in the U.S.

Conditions

• Rotator Cuff Injuries

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.