{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:08:15Z","timestamp":1793164095431,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,9,15]],"date-time":"2018-09-15T00:00:00Z","timestamp":1536969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011707","name":"PSP Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011707","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson's UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006041","name":"Innovate UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000320","name":"Alzheimer's Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000320","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The basis for clinical variation related to underlying progressive supranuclear palsy (PSP) pathology is unknown. We performed a genome\u2010wide association study (GWAS) to identify genetic determinants of PSP phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two independent pathological and clinically diagnosed PSP cohorts were genotyped and phenotyped to create Richardson syndrome (RS) and non\u2010RS groups. We carried out separate logistic regression GWASs to compare RS and non\u2010RS groups and then combined datasets to carry out a whole cohort analysis (RS\u2009=\u2009367, non\u2010RS\u2009=\u2009130). We validated our findings in a third cohort by referring to data from 100 deeply phenotyped cases from a recent GWAS. We assessed the expression\/coexpression patterns of our identified genes and used our data to carry out gene\u2010based association testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our lead single nucleotide polymorphism (SNP), rs564309, showed an association signal in both cohorts, reaching genome\u2010wide significance in our whole cohort analysis (odds ratio\u2009=\u20095.5, 95% confidence interval\u2009=\u20093.2\u201310.0,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.7\u2009\u00d7\u200910\n                      <jats:sup>\u22129<\/jats:sup>\n                      ). rs564309 is an intronic variant of the tripartite motif\u2010containing protein 11 (\n                      <jats:italic>TRIM11<\/jats:italic>\n                      ) gene, a component of the ubiquitin proteasome system (UPS). In our third cohort, minor allele frequencies of surrogate SNPs in high linkage disequilibrium with rs564309 replicated our findings. Gene\u2010based association testing confirmed an association signal at\n                      <jats:italic>TRIM11<\/jats:italic>\n                      . We found that TRIM11 is predominantly expressed neuronally, in the cerebellum and basal ganglia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Our study suggests that the\n                      <jats:italic>TRIM11<\/jats:italic>\n                      locus is a genetic modifier of PSP phenotype and potentially adds further evidence for the UPS having a key role in tau pathology, therefore representing a target for disease\u2010modifying therapies. Ann Neurol 2018;84:485\u2013496\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25308","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T09:45:56Z","timestamp":1533116756000},"page":"485-496","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Variation at the\n                    <i>TRIM11<\/i>\n                    locus modifies progressive supranuclear palsy phenotype"],"prefix":"10.1002","volume":"84","author":[{"given":"Edwin","family":"Jabbari","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences Institute of Neurology, University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Woodside","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences Institute of Neurology, University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela M. 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