| Title: | Identification of a Novel Genetic Marker for Risk of Degenerative Rotator Cuff Disease Surgery in the UK Biobank |
| Journal: | Journal of Bone and Joint Surgery |
| Published: | 12 May 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33979311/ |
| DOI: | https://doi.org/10.2106/jbjs.20.01474 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282705 |
| Citations: | 9 (6 in last 2 years) as of 8 Aug 2024 |
Publication 5163
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Abstract
BACKGROUND: While evidence indicates that familial predisposition influences the risk of developing degenerative rotator cuff disease (RCD), knowledge of specific genetic markers is limited. We conducted a genome-wide association study of RCD surgery using the UK Biobank, a prospective cohort of 500,000 people (40 to 69 years of age at enrollment) with genotype data.</p>
METHODS: Cases with surgery for degenerative RCD were identified using linked hospital records. The cases were defined as an International Classification of Diseases, Tenth Revision (ICD-10) code of M75.1 determined by a trauma/orthopaedic specialist and surgery consistent with RCD treatment. Cases were excluded if a diagnosis of traumatic injury had been made during the same hospital visit. For each case, up to 5 controls matched by age, sex, and follow-up time were chosen from the UK Biobank. Analyses were limited to European-ancestry individuals who were not third-degree or closer relations. We used logistic regression to test for genetic association of 674,405 typed and >10 million imputed markers, after adjusting for age, sex, population principal components, and follow-up.</p>
RESULTS: We identified 2,917 RCD surgery cases and 14,158 matched controls. We observed 1 genome-wide significant signal (p < 5 × 10-8) for a novel locus tagged by rs2237352 in the CREB5 gene on chromosome 7 (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.11 to 1.24). The single-nucleotide polymorphism (SNP) rs2237352 was imputed with a high degree of confidence (info score = 0.9847) and is common, with a minor allele frequency of 47%. After expanding the control sample to include additional unmatched non-cases, rs2237352 and another SNP in the CREB5 gene, rs12700903, were genome-wide significant. We did not detect genome-wide significant signals at loci associated with RCD in previous studies.</p>
CONCLUSIONS: We identified a novel association between a variant in the CREB5 gene and RCD surgery. Validation of this finding in studies with imaging data to confirm diagnoses will be an important next step.</p>
CLINICAL RELEVANCE: Identification of genetic RCD susceptibility markers can guide understanding of biological processes in rotator cuff degeneration and help inform disease risk in the clinical setting.</p>
LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.</p>
20 Keywords
- Adult
- Aged
- Biological Specimen Banks
- Biomarkers
- Case-Control Studies
- Cyclic AMP Response Element-Binding Protein A
- Female
- Follow-Up Studies
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Middle Aged
- Orthopedic Procedures
- Polymorphism, Single Nucleotide
- Prospective Studies
- Risk Assessment
- Rotator Cuff
- Rotator Cuff Injuries
- United Kingdom
8 Authors
- Elizabeth L. Yanik
- Jay D. Keener
- Shiow J. Lin
- Graham A. Colditz
- Rick W. Wright
- Bradley A. Evanoff
- Nitin B. Jain
- Nancy L. Saccone
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