Unique genetic and risk-factor profiles in clusters of major depressive disorder-related multimorbidity trajectories
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.
Authors
- Sarah Bonk
- András Millinghoffer
- Kevin Kirchner
- Carsten Oliver Schmidt (ORCID: https://orcid.org/0000-0001-5266-9396)
- Xénia Gonda (ORCID: https://orcid.org/0000-0001-9015-4203)
- Gábor Hullám (ORCID: https://orcid.org/0000-0002-4765-2351)
- Mikko Kuokkanen
- Péter Antal (ORCID: https://orcid.org/0000-0002-4370-2198)
- Josep Roca (ORCID: https://orcid.org/0000-0003-4768-8722)
- Hannu Mäkinen
- Isaac Cano (ORCID: https://orcid.org/0000-0003-2938-7459)
- Gabriella Juhász (ORCID: https://orcid.org/0000-0002-5975-4267)
- András Gézsi (ORCID: https://orcid.org/0000-0003-1022-6356)
- Nóra Eszlári (ORCID: https://orcid.org/0000-0003-4913-028X)
- Linda Garvert (ORCID: https://orcid.org/0000-0001-9067-8170)
- Bence Bolgár (ORCID: https://orcid.org/0000-0002-9561-1095)
- Sandra Van der Auwera (ORCID: https://orcid.org/0000-0002-1757-7768)
- Tamás Nagy
- Teemu Paajanen (ORCID: https://orcid.org/0000-0003-3499-4800)
- Zsófia Gál (ORCID: https://orcid.org/0000-0002-9441-1497)
- Rubèn González (ORCID: https://orcid.org/0000-0001-7330-9621)
Institutions
- Semmelweis University (HU)
- University of Helsinki (FI)
- Universitätsmedizin Greifswald (DE)
- German Center for Neurodegenerative Diseases (DE)
- The University of Texas Rio Grande Valley (US)
- Budapest University of Technology and Economics (HU)
- Finnish Institute for Health and Welfare (FI)
- Fundació Clínic per a la Recerca Biomèdica (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-21
- DOI
- https://doi.org/10.1038/s41467-024-51467-7
- Citations
- 13
- Primary Topic
- Mental Health Research Topics
- Type
- article
- Field-Weighted Citation Impact
- 6.60
Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- Semmelweis Egyetem
- Bundesministerium für Bildung und Forschung
- Magyar Tudományos Akadémia
- China Scholarship Council
- Universität Greifswald
- Nemzeti Kutatási, Fejlesztési és Innovaciós Alap