{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:11:50Z","timestamp":1788981110757,"version":"build-2803163510"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003921","name":"Department of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vestibular schwannomas are benign nerve sheath tumours that arise on the vestibulocochlear nerves. Vestibular schwannomas are known to occur in the context of tumour predisposition syndromes NF2-related and LZTR1-related schwannomatosis. However, the majority of vestibular schwannomas present sporadically without identification of germline pathogenic variants.<\/jats:p>\n                  <jats:p>To identify novel genetic associations with risk of vestibular schwannoma development, we conducted a genome-wide association study in a cohort of 911 sporadic vestibular schwannoma cases collated from the neurofibromatosis type 2 genetic testing service in the north-west of England, UK and 5500 control samples from the UK Biobank resource. One risk locus reached genome-wide significance in our association analysis (9p21.3, rs1556516, P = 1.47 \u00d7 10\u221213, odds ratio = 0.67, allele frequency = 0.52).<\/jats:p>\n                  <jats:p>9p21.3 is a genome-wide association study association hotspot, and a number of genes are localized to this region, notably CDKN2B-AS1 and CDKN2A\/B, also referred to as the INK4 locus. Dysregulation of gene products within the INK4 locus have been associated with multiple pathologies and the genes in this region have been observed to directly impact the expression of one another. Recurrent associations of the INK4 locus with components of well-described oncogenic pathways provides compelling evidence that the 9p21.3 region is truly associated with risk of vestibular schwannoma tumorigenesis.<\/jats:p>","DOI":"10.1093\/brain\/awac478","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T06:41:32Z","timestamp":1671691292000},"page":"2861-2868","source":"Crossref","is-referenced-by-count":14,"title":["Genome-wide association analysis identifies a susceptibility locus for sporadic vestibular schwannoma at 9p21"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5693-4932","authenticated-orcid":false,"given":"Katherine V","family":"Sadler","sequence":"first","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre (MAHSC) , Manchester M13 9WL , UK"},{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4659-031X","authenticated-orcid":false,"given":"John","family":"Bowes","sequence":"additional","affiliation":[{"name":"Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie F","family":"Rowlands","sequence":"additional","affiliation":[{"name":"Division of Genetics and Epidemiology, Institute of Cancer Research , Sutton, London SM2 5NG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Perez-Becerril","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre (MAHSC) , Manchester M13 9WL , UK"},{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Mwee","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T","family":"King","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and Neuroradiology Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Sciences Centre (MAHSC) , Manchester M6 8HD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and Neuroradiology Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Sciences Centre (MAHSC) , Manchester M6 8HD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar N","family":"Pathmanaban","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and Neuroradiology Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Sciences Centre (MAHSC) , Manchester M6 8HD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Hammerbeck-Ward","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and Neuroradiology Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Sciences Centre (MAHSC) , Manchester M6 8HD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon K W","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Manchester Royal Infirmary, Manchester Academic Health Sciences Centre (MAHSC), University of Manchester , Manchester M13 9WL , UK"},{"name":"Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon R","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Manchester Royal Infirmary, Manchester Academic Health Sciences Centre (MAHSC), University of Manchester , Manchester M13 9WL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky","family":"Williams","sequence":"additional","affiliation":[{"name":"Brain Tumour Biobank, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre (MAHSC) , Manchester M6 8HD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathal John","family":"Hannan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and Neuroradiology Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Sciences Centre (MAHSC) , Manchester M6 8HD , UK"},{"name":"Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology Medicine and Health, University of Manchester , Manchester M13 9PL , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6831-6990","authenticated-orcid":false,"given":"Daniel","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, and Neuroradiology Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Sciences Centre (MAHSC) , Manchester M6 8HD , 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