{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:13:00Z","timestamp":1772169180750,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.23013.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000}}],"reference-count":21,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["218497"],"award-info":[{"award-number":["218497"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["084779"],"award-info":[{"award-number":["084779"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>Background Hearing loss is a risk factor for developing auditory hallucinations and other psychosis symptoms. To date, very little research has investigated hearing loss in individuals with a high genetic risk of developing schizophrenia and other types of psychosis. 13 copy number variant (CNV) loci are robustly associated with an increased risk of schizophrenia. Of these, microdeletions at 22q11.2 often lead to some hearing loss, and mouse models of this CNV display impaired auditory functioning. We hypothesise that individuals who have a high genetic risk of schizophrenia may also experience hearing problems. This scoping review will explore whether the 13 schizophrenia-associated CNVs are related to hearing problems, including peripheral hearing loss and other auditory problems, in humans and related mouse models. Methods Our scoping review will follow guidelines provided by the Joanna Briggs Institute and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. A systematic search will be completed using PubMed (MEDLINE), Embase, PsychINFO, and Cochrane Library databases, as well as other sources to identify relevant grey literature. Search terms will include all commonly used synonyms for hearing loss and problems with auditory perception, and both human and mouse studies that describe relevant CNVs will be included. Search lists will be screened by two authors independently, according to eligibility criteria, and data will be extracted and summarised using a narrative approach. Conclusions To our knowledge, this will be the first scoping review to explore auditory functioning across all CNVs that confer high schizophrenia risk. Looking ahead, if hearing problems are a clinical feature in these groups (including humans and related mouse models), they may serve as useful genetic models for future mechanistic studies.<\/ns3:p>","DOI":"10.12688\/wellcomeopenres.23013.2","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T06:30:07Z","timestamp":1734330607000},"page":"546","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hearing problems in humans and mouse models with rare copy number variants associated with schizophrenia: a scoping review protocol"],"prefix":"10.12688","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7440-7095","authenticated-orcid":false,"given":"Stephen","family":"Murtough","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Panconesi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemary","family":"Abidoph","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius","family":"Cotic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0592-9428","authenticated-orcid":false,"given":"Daisy","family":"Mills","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8577-9380","authenticated-orcid":false,"given":"Alvin","family":"Richards-Belle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0279-0793","authenticated-orcid":false,"given":"Maria","family":"Richards-Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noushin","family":"Saadullah Khani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1139-4790","authenticated-orcid":false,"given":"Lauren","family":"Varney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer F","family":"Linden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elvira","family":"Bramon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"22-35","DOI":"10.1038\/s41582-023-00904-0","article-title":"Schizophrenia: from neurochemistry to circuits, symptoms and treatments.","volume":"20","author":"O Howes","year":"2024","journal-title":"Nat Rev 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hearing impairment: how informed are clinicians?","volume":"49","author":"T Marschall","year":"2023","journal-title":"Schizophr Bull."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"502-8","DOI":"10.1038\/s41586-022-04434-5","article-title":"Mapping genomic loci implicates genes and synaptic biology in schizophrenia.","volume":"604","author":"V Trubetskoy","year":"2022","journal-title":"Nature."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"509-16","DOI":"10.1038\/s41586-022-04556-w","article-title":"Rare coding variants in ten genes confer substantial risk for schizophrenia.","volume":"604","author":"T Singh","year":"2022","journal-title":"Nature."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"27-35","DOI":"10.1038\/ng.3725","article-title":"Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects.","volume":"49","author":"C Marshall","year":"2017","journal-title":"Nat 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for Scoping Reviews (PRISMA-ScR): checklist and explanation.","volume":"169","author":"A Tricco","year":"2018","journal-title":"Ann Intern Med."},{"key":"ref-20","doi-asserted-by":"publisher","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement.","volume":"4","author":"D Moher","year":"2015","journal-title":"Syst Rev."},{"key":"ref-21","article-title":"Hearing problems in humans and mouse models with rare copy number variants associated with schizophrenia: a scoping review protocol","author":"S Murtough","year":"2024"}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-546\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-546\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-546\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T11:40:11Z","timestamp":1734435611000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-546\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,16]]},"references-count":21,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.23013.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/wellcomeopenres.23013.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.25944.r115733","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.25944.r115734","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.25944.r115733","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,16]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-546\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.25343.r103673, Esra Sefik, Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey, 25 Oct 2024, version 1, 3 approved with reservations","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-546\/v1#referee-response-103673","order":0,"name":"referee-response-103673","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Stephen Murtough<\/b>; \n<i>Posted: 09 Dec 2024<\/i>; Thank you, Esra, for your kind and thoughtful review. We appreciate all your points for improvement, and our responses are below.  We agree that our study is not well designed to test our previously specified hypothesis. We have amended the abstract text to include the following: \u201cWe hypothesise that individuals who have a high genetic risk of schizophrenia may also experience hearing problems\u201d. We have also amended the main text to reflect the new hypothesis. &nbsp; We appreciate your suggestion to formally test for correlations between hearing problems and psychosis symptoms. Our assumption, based on a preliminarily literature search, is that data will not be available in sufficient detail to allow for this approach, and therefore we have decided not to include this in our protocol. If we find that sufficient data are available, however, we will update the study protocol to include this information. &nbsp; We agree that 95% confidence intervals should be added to Table 1, and that the odds ratio for the 3q29 deletion should be amended to \u201cinfinite\u201d, as described in the original publication by Marshall \n<i>et al<\/i>. We have made these changes to Table 1 in the manuscript. &nbsp; We agree that search strategies should be provided for all 13 schizophrenia-associated CNVs. We have provided these as Appendix 2 in the extended data, and we have referred to this in the main text. &nbsp; We welcome your suggestion to provide more detail about the meta-analysis strategy. Based on a preliminary literature search, our assumption is that insufficient data will be available to complete a meta-analysis. Therefore, we are inclined to keep our protocol focused as a scoping review, and we have removed all mentions in the main text about performing a meta-analysis. If we find that sufficient data are available after the full literature search, we will update the study protocol with this information.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-546\/v2#referee-comment-5953","order":1,"name":"referee-comment-5953","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.25343.r102571, Biju Viswanath, National Institute of Mental Health and Neurosciences, Bengaluru, 04 Nov 2024, version 1, 3 approved with reservations","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-546\/v1#referee-response-102571","order":2,"name":"referee-response-102571","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Stephen Murtough<\/b>; \n<i>Posted: 09 Dec 2024<\/i>; Thank you, Biju, for your helpful comments. We provide our responses below.  The 2017 publication from Marshall \n<i>et al<\/i> is a landmark study from the CNV and Schizophrenia Working Groups within the Psychiatric Genomics Consortium. &nbsp;This is the most recent and comprehensive genome-wide analysis of CNVs that increase risk of schizophrenia, comprising 21,094 cases and 20,227 controls. We consider this to be the most robust publication to base our scoping review on, although we agree that there is substantial bias for European samples. To mark this as a limitation, we have included the following sentence in the main text:  \u201cWe note, however, that these CNVs were identified using European samples, and other schizophrenia-associated CNVs in individuals with different ancestries are likely to be under-reported.\u201d &nbsp; We appreciate your comments regarding the language of articles to be included in the review. To clarify, no language restrictions will be applied during the literature search, although searches will be performed using English. Any articles that are not written in English will be translated into English using DeepL, which is an online translating software. To provide clarity for the reader, we have added an extra sentence to the main text, confirming that the literature search will be performed using English. &nbsp; We thank you for your suggestion to include a flow chart as a visual aid. In this instance, we have decided not to include this, as we consider the protocol to be clear and concise in its current format. However, we intend to produce a detailed flow chart for the scoping review publication, which will include information about the number of studies identified during the selection process. &nbsp;","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-546\/v2#referee-comment-5954","order":3,"name":"referee-comment-5954","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.25944.r115733, Clara S Humpston, University of York, Heslington, 17 Dec 2024, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-546\/v2#referee-response-115733","order":4,"name":"referee-response-115733","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by Wellcome [084779 and 218497]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}