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Genetic investigations of 100 inherited cardiac disease-related genes in deceased individuals with schizophrenia

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Abstract

Cardiac diseases and sudden cardiac death (SCD) are more prevalent in individuals diagnosed with schizophrenia compared to the general population, with especially coronary artery disease (CAD) as the major cardiovascular cause of death. Antipsychotic medications, genetics, and lifestyle factors may contribute to the increased SCD in individuals with schizophrenia. The role of antipsychotic medications and lifestyle factors have been widely investigated, while the genetic predisposition to inherited cardiac diseases in schizophrenia is poorly understood. In this study, we examined 100 genes associated with inherited cardiomyopathies and cardiac channelopathies in 97 deceased individuals diagnosed with schizophrenia for the prevalence of genetic variants associated with SCD. The deceased individuals had various causes of death and were included in the SURVIVE project, a prospective, autopsy-based study of mentally ill individuals in Denmark. This is the first study of multiple inherited cardiac disease-related genes in deceased individuals with diagnosed schizophrenia to shed light on the genetic predisposition to SCD in individuals with schizophrenia. We found no evidence for an overrepresentation of rare variants with high penetrance in inherited cardiac diseases, following the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG) consensus guidelines. However, we found that the deceased individuals had a statistically significantly increased polygenic burden caused by variants in the investigated heart genes compared to the general population. This indicates that common variants with smaller effects in heart genes may play a role in schizophrenia.

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Acknowledgements

We would like to thank the next-of-kin of study participants for providing consent for inclusion in this study, Anja Ladegaard Jørgensen for technical assistance in the laboratory, and the people involved in the SURVIVE project, including medical doctors, secretaries, and forensic and laboratory technicians at the forensic medicine departments in Odense, Aarhus, and Copenhagen, Denmark.

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    Authors and Affiliations

    1. Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

      Sofie Lindgren Christiansen, Jeppe Dyrberg Andersen, Gonçalo Espregueira Themudo, Christin Løth Hertz & Niels Morling

    2. Chromosome Laboratory, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

      Sofie Lindgren Christiansen

    3. CIIMAR - Interdisciplinary Centre of Marine and Environmental, Research of the University of Porto, Terminal de Cruzeiros Do Porto, de Leixões, Avenida General Norton de Matos, 4450-208, Matosinhos, S/N, Portugal

      Gonçalo Espregueira Themudo

    4. Novo Nordisk A/S, Vandtårnsvej, 108-110 2860, Søborg, Denmark

      Christin Løth Hertz

    5. Section of Forensic Pathology, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

      Johannes Rødbro Busch, Martin Roest Christensen, Kristine Boisen Olsen & Jytte Banner

    6. Department of Forensic Medicine, Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark

      Martin Roest Christensen

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    Christiansen, S.L., Andersen, J.D., Themudo, G.E. et al. Genetic investigations of 100 inherited cardiac disease-related genes in deceased individuals with schizophrenia. Int J Legal Med 135, 1395–1405 (2021). https://doi.org/10.1007/s00414-021-02595-y

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