{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T15:31:10Z","timestamp":1789831870591,"version":"4.0.1"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7,21]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>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 &gt;10 million imputed markers, after adjusting for age, sex, population principal components, and follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We identified 2,917 RCD surgery cases and 14,158 matched controls. We observed 1 genome-wide significant signal (p &lt; 5 \u00d7 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      ) for a novel locus tagged by rs2237352 in the\n                      <jats:italic toggle=\"yes\">CREB5<\/jats:italic>\n                      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\n                      <jats:italic toggle=\"yes\">CREB5<\/jats:italic>\n                      gene, rs12700903, were genome-wide significant. We did not detect genome-wide significant signals at loci associated with RCD in previous studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      We identified a novel association between a variant in the\n                      <jats:italic toggle=\"yes\">CREB5<\/jats:italic>\n                      gene and RCD surgery. Validation of this finding in studies with imaging data to confirm diagnoses will be an important next step.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Relevance:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence:<\/jats:title>\n                    <jats:p>\n                      Prognostic\n                      <jats:underline>Level III<\/jats:underline>\n                      . See Instructions for Authors for a complete description of levels of evidence.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.2106\/jbjs.20.01474","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T15:01:13Z","timestamp":1620831673000},"page":"1259-1267","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":16,"title":["Identification of a Novel Genetic Marker for Risk of Degenerative Rotator Cuff Disease Surgery in the UK Biobank"],"prefix":"10.2106","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5835-0201","authenticated-orcid":false,"given":"Elizabeth L.","family":"Yanik","sequence":"first","affiliation":[{"name":"Departments of Orthopaedic Surgery (E.L.Y., J.D.K., and R.W.W.), Surgery (E.L.Y. and G.A.C.), Genetics (S.J.L. and N.L.S.), and General Medical Studies (B.A.E.), Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1665-4346","authenticated-orcid":false,"given":"Jay D.","family":"Keener","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery (E.L.Y., J.D.K., and R.W.W.), Surgery (E.L.Y. and G.A.C.), Genetics (S.J.L. and N.L.S.), and General Medical Studies (B.A.E.), Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4292-1751","authenticated-orcid":false,"given":"Shiow J.","family":"Lin","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery (E.L.Y., J.D.K., and R.W.W.), Surgery (E.L.Y. and G.A.C.), Genetics (S.J.L. and N.L.S.), and General Medical Studies (B.A.E.), Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7307-0291","authenticated-orcid":false,"given":"Graham A.","family":"Colditz","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery (E.L.Y., J.D.K., and R.W.W.), Surgery (E.L.Y. and G.A.C.), Genetics (S.J.L. and N.L.S.), and General Medical Studies (B.A.E.), Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4018-7132","authenticated-orcid":false,"given":"Rick W.","family":"Wright","sequence":"additional","affiliation":[{"name":"Departments of Orthopaedic Surgery (E.L.Y., J.D.K., and R.W.W.), Surgery (E.L.Y. and G.A.C.), Genetics (S.J.L. and N.L.S.), and General Medical Studies (B.A.E.), Washington University School of Medicine, St. Louis, 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