Whole-genome sequencing analysis of clozapine-induced myocarditis
Whole-genome sequencing analysis of clozapine-induced myocarditis
ABSTRACT One of the concerns limiting the use of clozapine in schizophrenia treatment is the risk of rare but potentially fatal myocarditis. Our previous genome-wide association study and human leucocyte antigen analyses identified putative loci associated with clozapine-induced myocarditis. However, the contribution of DNA variation in cytochrome P450 genes, copy number variants and rare deleterious variants have not been investigated. We explored these unexplored classes of DNA variation using whole-genome sequencing data from 25 cases with clozapine-induced myocarditis and 25 demographically-matched clozapine-tolerant control subjects. We identified 15 genes based on rare variant gene-burden analysis (MLLT6, CADPS, TACC2, L3MBTL4, NPY, SLC25A21, PARVB, GPR179, ACAD9, NOL8, C5orf33, FAM127A, AFDN, SLC6A11, PXDN) nominally associated (p<0.05) with clozapine-induced myocarditis. Of these genes, 13 were expressed in human myocardial tissue. Although independent replication of these findings is required, our study provides preliminary insights into the potential role of rare genetic variants in susceptibility to clozapine-induced myocarditis.
Jayaram Mahesh、Thomas Naveen、Bousman Chad A、Narang Ankita、McNeil John J、Stowe Robert、Crockford David、Pantelis Christos、Sellmer Rory、Lacaze Paul、Greenway Steven C.、Ronaldson Kathlyn J
Adult Mental Health Rehabilitation Unit, North Western Mental Health, Melbourne Health, Western Health, Sunshine Hospital||Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Western Centre for Health & EducationAdult Mental Health Rehabilitation Unit, North Western Mental Health, Melbourne Health, Western Health, Sunshine Hospital||Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Western Centre for Health & EducationDepartment of Medical Genetics, University of Calgary||Department of Psychiatry, University of Calgary||Alberta Children?ˉs Hospital Research Institute, Cumming School of Medicine, University of Calgary||Department of Physiology & Pharmacology, University of Calgary||Hotchkiss Brain Institute, Cumming School of Medicine, University of CalgaryDepartment of Medical Genetics, University of CalgaryDepartment of Epidemiology and Preventive Medicine, Monash UniversityDepartments of Psychiatry and Neurology (Medicine), Neuropsychiatry Program, and Djavad Mowafaghian Centre for Brain Health, University of British ColumbiaDepartment of Psychiatry, University of CalgaryAdult Mental Health Rehabilitation Unit, North Western Mental Health, Melbourne Health, Western Health, Sunshine Hospital||Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Western Centre for Health & EducationDepartment of Psychiatry, University of CalgaryDepartment of Epidemiology and Preventive Medicine, Monash UniversityDepartment of Pediatrics, Cumming School of Medicine, University of Calgary||Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary||Alberta Children?ˉs Hospital Research Institute, Cumming School of Medicine, University of Calgary||Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary||Libin Cardiovascular Institute, Cumming School of Medicine, University of CalgaryDepartment of Epidemiology and Preventive Medicine, Monash University
医学研究方法基础医学神经病学、精神病学
Jayaram Mahesh,Thomas Naveen,Bousman Chad A,Narang Ankita,McNeil John J,Stowe Robert,Crockford David,Pantelis Christos,Sellmer Rory,Lacaze Paul,Greenway Steven C.,Ronaldson Kathlyn J.Whole-genome sequencing analysis of clozapine-induced myocarditis[EB/OL].(2025-03-28)[2025-08-02].https://www.medrxiv.org/content/10.1101/2021.07.26.21261157.点此复制
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