Identification of a Novel Genetic Marker for Risk of Degenerative Rotator Cuff Disease Surgery in the UK Biobank
| Autor: | Nitin B. Jain, Elizabeth L. Yanik, Bradley A. Evanoff, Rick W. Wright, Jay D. Keener, Shiow J Lin, Nancy L. Saccone, Graham A. Colditz |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Genetic Markers medicine.medical_specialty Population Disease Cyclic AMP Response Element-Binding Protein A Polymorphism Single Nucleotide Risk Assessment Article Rotator Cuff Injuries Rotator Cuff 03 medical and health sciences 0302 clinical medicine medicine Humans Genetic Predisposition to Disease Orthopedic Procedures Orthopedics and Sports Medicine Clinical significance Prospective Studies education Prospective cohort study Aged Biological Specimen Banks Genetic association 030222 orthopedics education.field_of_study business.industry 030229 sport sciences General Medicine Odds ratio Middle Aged United Kingdom Confidence interval Surgery Minor allele frequency Case-Control Studies Female business Biomarkers Follow-Up Studies Genome-Wide Association Study |
| Zdroj: | J Bone Joint Surg Am |
| ISSN: | 1535-1386 0021-9355 |
| DOI: | 10.2106/jbjs.20.01474 |
| Popis: | 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. 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. 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. 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. 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. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. |
| Databáze: | OpenAIRE |
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