Gézsi, András and Van der Auwera, Sandra and Mäkinen, Hannu and Eszlári, Nóra and Hullám, Gábor István and Nagy, Tamás and Bonk, Sarah and González-Colom, Rubèn and Gonda, Xénia and Garvert, Linda and Paajanen, Teemu and Gál, Zsófia and Kirchner, Kevin and Millinghoffer, András Dániel and Schmidt, Carsten O. and Bolgár, Bence Márton and Roca, Josep and Cano, Isaac and Kuokkanen, Mikko and Antal, Péter and Juhász, Gabriella (2024) Unique genetic and risk-factor profiles in clusters of major depressive disorder-related multimorbidity trajectories. NATURE COMMUNICATIONS, 15 (1). ISSN 2041-1723
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Abstract
The heterogeneity and complexity of symptom presentation, comorbidities and genetic factors pose challenges to the identification of biological mechanisms underlying complex diseases. Current approaches used to identify biological subtypes of major depressive disorder (MDD) mainly focus on clinical characteristics that cannot be linked to specific biological models. Here, we examined multimorbidities to identify MDD subtypes with distinct genetic and non-genetic factors. We leveraged dynamic Bayesian network approaches to determine a minimal set of multimorbidities relevant to MDD and identified seven clusters of disease-burden trajectories throughout the lifespan among 1.2 million participants from cohorts in the UK, Finland, and Spain. The clusters had clear protective- and risk-factor profiles as well as age-specific clinical courses mainly driven by inflammatory processes, and a comprehensive map of heritability and genetic correlations among these clusters was revealed. Our results can guide the development of personalized treatments for MDD based on the unique genetic, clinical and non-genetic risk-factor profiles of patients.
| Item Type: | Article |
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| Additional Information: | Department of Artificial Intelligence and Systems Engineering, Budapest University of Technology and Economics, Budapest, Hungary Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany German Centre for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany Department of Public Health and Welfare, Population Health Unit, Public Health Research Team, Finnish Institute for Health and Welfare, Helsinki, Finland Department of Pharmacodynamics, Faculty of Pharmaceutical Sciences, Semmelweis University, Budapest, Hungary NAP3.0-SE Neuropsychopharmacology Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary Clínic Barcelona, Fundació de Recerca Clinic Barcelona - Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Universitat de Barcelona, Barcelona, Spain Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary Abiomics Europe Ltd., Budapest, Hungary Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany Department of Human Genetics and South Texas Diabetes and Obesity Institute, School of Medicine at University of Texas Rio Grande Valley, Brownsville, TX, United States Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland Export Date: 3 September 2024 Correspondence Address: Juhasz, G.; Department of Pharmacodynamics, Hungary; email: juhasz.gabriella@semmelweis.hu |
| Subjects: | R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 13 Sep 2024 07:18 |
| Last Modified: | 13 Sep 2024 07:18 |
| URI: | https://real.mtak.hu/id/eprint/204775 |
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