{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T13:51:05Z","timestamp":1783086665503,"version":"3.54.6"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Fund for Academician Lin He New Medicine"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Second-generation antipsychotics (SGAs) play a critical role in current treatment of schizophrenia (SCZ). It has been observed that sinus bradycardia, rare but in certain situations life threatening adverse drug reaction, can be induced by SGAs across different schizophrenia populations. However, the roles of genetic factors in this phenomenon have not been studied yet. In the present study, a genome-wide association study of single nucleotide polymorphisms (SNPs) was performed on Chinese Han SCZ patients to identify susceptibility loci that were associated with sinus bradycardia induced by SGAs. This study applied microarray to obtain genotype profiles of 88 Han Chinese SCZ patients. Our results found that there were no SNPs had genome-wide significant association with sinus bradycardia induced by SGAs. The top GWAS hit located in gene <jats:italic>KIAA0247<\/jats:italic>, which mainly regulated by the tumor suppressor P53 and thus plays a role in carcinogenesis based on resent research and it should not be a susceptibility locus to sinus bradycardia induced by SGAs. Using gene-set functional analysis, we tested that if top 500 SNPs mapped genes were relevant to sinus bradycardia. The result of gene prioritization analysis showed <jats:italic>CTNNA3<\/jats:italic> was strongly correlated with sinus bradycardia, hinting it was a susceptibility gene of this ADR. Our study provides a preliminary study of genetic variants associated with sinus bradycardia induced by SGAs in Han Chinese SCZ patients. The discovery of a possible susceptibility gene shed light on further study of this adverse drug reaction in Han Chinese SCZ patients.<\/jats:p>","DOI":"10.1371\/journal.pone.0249997","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T17:31:54Z","timestamp":1619717514000},"page":"e0249997","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genome-wide association study of antipsychotic-induced sinus bradycardia in Chinese schizophrenia patients"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3843-8177","authenticated-orcid":true,"given":"Saizheng","family":"Weng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqian","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongyan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinliang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaonan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"issue":"5","key":"pone.0249997.ref001","doi-asserted-by":"crossref","first-page":"e151","DOI":"10.1371\/journal.pmed.0020151","article-title":"The global prevalence of schizophrenia","volume":"2","author":"D Bhugra","year":"2005","journal-title":"PLoS medicine"},{"key":"pone.0249997.ref002","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/epirev\/mxn001","article-title":"Schizophrenia: a concise overview of incidence, prevalence, and mortality","volume":"30","author":"J McGrath","year":"2008","journal-title":"Epidemiologic reviews"},{"key":"pone.0249997.ref003","doi-asserted-by":"crossref","first-page":"15067","DOI":"10.1038\/nrdp.2015.67","article-title":"Schizophrenia","volume":"1","author":"RS Kahn","year":"2015","journal-title":"Nature reviews Disease primers"},{"issue":"4","key":"pone.0249997.ref004","doi-asserted-by":"crossref","first-page":"421","DOI":"10.31887\/DCNS.2015.17.4\/aanticevic","article-title":"Emotional and cognitive dysregulation in schizophrenia and depression: understanding common and distinct behavioral and neural mechanisms","volume":"17","author":"A Anticevic","year":"2015","journal-title":"Dialogues in clinical neuroscience"},{"issue":"23","key":"pone.0249997.ref005","doi-asserted-by":"crossref","first-page":"3777","DOI":"10.1007\/s00018-009-0130-3","article-title":"Group II metabotropic glutamate receptors and schizophrenia","volume":"66","author":"JL Moreno","year":"2009","journal-title":"Cellular and molecular life sciences: CMLS"},{"issue":"7321","key":"pone.0249997.ref006","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nature09552","article-title":"Rethinking schizophrenia","volume":"468","author":"TR Insel","year":"2010","journal-title":"Nature"},{"issue":"8","key":"pone.0249997.ref007","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S2215-0366(16)00085-7","article-title":"Effects of first-generation antipsychotics versus second-generation antipsychotics on quality of life in schizophrenia: a double-blind, randomised study","volume":"3","author":"G Grunder","year":"2016","journal-title":"The lancet Psychiatry"},{"issue":"4","key":"pone.0249997.ref008","doi-asserted-by":"crossref","first-page":"252","DOI":"10.2174\/1871530315666150623092031","article-title":"Weight Gain and Metabolic Changes During Treatment with Antipsychotics and Antidepressants","volume":"15","author":"H Himmerich","year":"2015","journal-title":"Endocrine, metabolic & immune disorders drug targets"},{"issue":"3","key":"pone.0249997.ref009","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1002\/wps.20579","article-title":"Tardive dyskinesia risk with first- and second-generation antipsychotics in comparative randomized controlled trials: a meta-analysis","volume":"17","author":"M Carbon","year":"2018","journal-title":"World psychiatry: official journal of the World Psychiatric Association"},{"issue":"5","key":"pone.0249997.ref010","first-page":"421","article-title":"The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review","volume":"28","author":"J Peuskens","year":"2014","journal-title":"CNS drugs"},{"key":"pone.0249997.ref011","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jns.2018.02.011","article-title":"Genetics of tardive dyskinesia: Promising leads and ways forward","volume":"389","author":"CC Zai","year":"2018","journal-title":"Journal of the neurological sciences"},{"key":"pone.0249997.ref012","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3389\/fpsyt.2018.00157","article-title":"The Importance of Social Cognition in Improving Functional Outcomes in Schizophrenia","volume":"9","author":"A Javed","year":"2018","journal-title":"Frontiers in psychiatry"},{"issue":"5","key":"pone.0249997.ref013","doi-asserted-by":"crossref","first-page":"497 e1","DOI":"10.1016\/j.genhosppsych.2013.12.005","article-title":"Amisulpride and symptomatic bradycardia: a case report","volume":"37","author":"LC Huang","year":"2015","journal-title":"General hospital psychiatry"},{"key":"pone.0249997.ref014","article-title":"Evaluating and managing bradycardia","author":"S Sidhu","year":"2019","journal-title":"Trends in cardiovascular medicine"},{"issue":"5","key":"pone.0249997.ref015","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1161\/CIRCULATIONAHA.107.706887","article-title":"Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia","volume":"116","author":"E Nof","year":"2007","journal-title":"Circulation"},{"issue":"2","key":"pone.0249997.ref016","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19020634","article-title":"Sinus Bradycardia in Carriers of the SCN5A-1795insD Mutation: Unraveling the Mechanism through Computer Simulations","volume":"19","author":"R Wilders","year":"2018","journal-title":"International journal of molecular sciences"},{"issue":"11","key":"pone.0249997.ref017","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1136\/jmg.2004.028993","article-title":"Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients","volume":"42","author":"AV Postma","year":"2005","journal-title":"Journal of medical genetics"},{"issue":"4","key":"pone.0249997.ref018","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/ng.781","article-title":"A rare variant in MYH6 is associated with high risk of sick sinus syndrome","volume":"43","author":"H Holm","year":"2011","journal-title":"Nat Genet"},{"key":"pone.0249997.ref019","doi-asserted-by":"crossref","first-page":"648","DOI":"10.3389\/fgene.2019.00648","article-title":"Functional Characterization of Rare Variants in the SHOX2 Gene Identified in Sinus Node Dysfunction and Atrial Fibrillation","volume":"10","author":"S Hoffmann","year":"2019","journal-title":"Frontiers in genetics"},{"issue":"9167","key":"pone.0249997.ref020","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/S0140-6736(05)75101-1","article-title":"Declaration of Helsinki","volume":"353","author":"D Human","year":"1999","journal-title":"Lancet"},{"key":"pone.0249997.ref021","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"CC Chang","year":"2015","journal-title":"GigaScience"},{"issue":"7422","key":"pone.0249997.ref022","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature11632","article-title":"An integrated map of genetic variation from 1,092 human genomes","volume":"491","author":"C Genomes Project","year":"2012","journal-title":"Nature"},{"issue":"1","key":"pone.0249997.ref023","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nmeth.2307","article-title":"Improved whole-chromosome phasing for disease and population genetic studies","volume":"10","author":"O Delaneau","year":"2013","journal-title":"Nature methods"},{"key":"pone.0249997.ref024","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1186\/1756-0500-7-901","article-title":"Genotype harmonizer: automatic strand alignment and format conversion for genotype data integration","volume":"7","author":"P Deelen","year":"2014","journal-title":"BMC research notes"},{"issue":"6","key":"pone.0249997.ref025","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1534\/g3.111.001198","article-title":"Genotype imputation with thousands of genomes","volume":"1","author":"B Howie","year":"2011","journal-title":"G3"},{"issue":"Web Server issue","key":"pone.0249997.ref026","doi-asserted-by":"crossref","first-page":"W305","DOI":"10.1093\/nar\/gkp427","article-title":"ToppGene Suite for gene list enrichment analysis and candidate gene prioritization","volume":"37","author":"J Chen","year":"2009","journal-title":"Nucleic acids research"},{"issue":"12","key":"pone.0249997.ref027","first-page":"4978","article-title":"Genetic mechanisms underlying spermatic and testicular traits within and among cattle breeds: systematic review and prioritization of GWAS results","volume":"96","author":"PAS Fonseca","year":"2018","journal-title":"Journal of animal science"},{"issue":"Database issue","key":"pone.0249997.ref028","doi-asserted-by":"crossref","first-page":"D1049","DOI":"10.1093\/nar\/gku1179","article-title":"Gene Ontology Consortium: going forward","volume":"43","author":"C Gene Ontology","year":"2015","journal-title":"Nucleic acids research"},{"issue":"D1","key":"pone.0249997.ref029","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"D Szklarczyk","year":"2019","journal-title":"Nucleic acids research"},{"issue":"4","key":"pone.0249997.ref030","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1111\/cas.13539","article-title":"KIAA0247 inhibits growth, migration, invasion of non-small-cell lung cancer through regulating the Notch pathway","volume":"109","author":"Y Xu","year":"2018","journal-title":"Cancer science"},{"key":"pone.0249997.ref031","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/10_2016_40","article-title":"Protein-Protein Interface and Disease: Perspective from Biomolecular Networks","volume":"160","author":"G Hu","year":"2017","journal-title":"Advances in biochemical engineering\/biotechnology"},{"issue":"4","key":"pone.0249997.ref032","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.sbi.2005.06.001","article-title":"Protein-protein interactions in human disease","volume":"15","author":"DP Ryan","year":"2005","journal-title":"Current opinion in structural biology"},{"issue":"9","key":"pone.0249997.ref033","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.euroneuro.2009.04.008","article-title":"Antipsychotics in children and adolescents: increasing use, evidence for efficacy and safety concerns","volume":"19","author":"B Vitiello","year":"2009","journal-title":"European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology"},{"issue":"1","key":"pone.0249997.ref034","article-title":"Direct and indirect effects of psychopharmacological treatment on the cardiovascular system","volume":"36","author":"KG Kahl","year":"2018","journal-title":"Hormone molecular biology and clinical investigation"},{"issue":"2","key":"pone.0249997.ref035","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1056\/NEJMoa052475","article-title":"Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel","volume":"354","author":"R Milanesi","year":"2006","journal-title":"N Engl J Med"},{"issue":"12","key":"pone.0249997.ref036","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1111\/j.1540-8167.2010.01844.x","article-title":"A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews","volume":"21","author":"A Laish-Farkash","year":"2010","journal-title":"Journal of cardiovascular electrophysiology"},{"issue":"6","key":"pone.0249997.ref037","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1111\/ene.13607","article-title":"Ryanodine receptor type 3 (RYR3) as a novel gene associated with a myopathy with nemaline bodies","volume":"25","author":"Y Nilipour","year":"2018","journal-title":"European journal of neurology"},{"issue":"6310","key":"pone.0249997.ref038","doi-asserted-by":"crossref","DOI":"10.1126\/science.aah5324","article-title":"Structural basis for the gating mechanism of the type 2 ryanodine receptor RyR2","volume":"354","author":"W Peng","year":"2016","journal-title":"Science"},{"issue":"13","key":"pone.0249997.ref039","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.2169\/internalmedicine.9843-17","article-title":"Bradycardia Is a Specific Phenotype of Catecholaminergic Polymorphic Ventricular Tachycardia Induced by RYR2 Mutations","volume":"57","author":"K Miyata","year":"2018","journal-title":"Internal medicine"},{"issue":"3","key":"pone.0249997.ref040","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00439-002-0857-5","article-title":"Assessment of the CTNNA3 gene encoding human \u03b1T-catenin regarding its involvement in dilated cardiomyopathy","volume":"112","author":"B Janssens","year":"2003","journal-title":"Human Genetics"},{"issue":"3","key":"pone.0249997.ref041","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1093\/eurheartj\/ehs373","article-title":"Mutations in the area composita protein alphaT-catenin are associated with arrhythmogenic right ventricular cardiomyopathy","volume":"34","author":"J van Hengel","year":"2013","journal-title":"European heart journal"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0249997","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T17:32:39Z","timestamp":1619717559000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0249997"}},"subtitle":[],"editor":[{"given":"Yun","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,4,29]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0249997","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,29]]}}}