Berlin Research Initiative for Diagnostics, Genetics and Environmental Factors in Schizophrenia (BRIDGE-S)
Molecular Biology and Physiology of Neurons and Glial Cells
Final Report Abstract
BRIDGE-S aims to explore the genetic, environmental, and phenotypic factors contributing to schizophrenia (SCZ). Building on the foundational Berlin Psychosis Study (BePS), BRIDGE-S refines risk prediction and subtyping through enhanced phenotyping and a modular study design. Cohort Development: The study aimed to recruit a total of 1,000 SCZ cases and 1,000 unaffected control participants. By November 2024, the control target was achieved (1,171 controls) and 852 SCZ cases were recruited into the study. The recruitment of new participants was completed in November 2024, data collection is expected to end in March 2025. International extensions are ongoing in Vietnam, Nigeria, and Greece (not financially supported by this grant). Data Collection: Participants undergo a mandatory core assessment (e.g., saliva for genotyping and comprehensive questionnaires that cover a broad range of environmental exposures, sociodemographic, clinical and other mental health-related variables) and optional modules (e.g., clinical interviews, neurocognitive testing using the CANTAB schizophrenia battery). Modular (mandatory core assessment, later deep phenotyping that is optional) and remote participation (from home) approaches increased accessibility while maintaining high-quality data collection. Genomic and Phenotypic Data: Genotyping on the Illumina Infinium Global Screening Array (GSA) provides detailed SNP-level data that allows us to compute individual-level polygenic risk scores (PRS) for schizophrenia. Phenotypic data includes neurocognitive and clinical assessments, exploring domains like emotion recognition, memory, and psychomotor speed. Quantitative measures such as the previously proposed environmental risk score (ERS) for psychosis were derived to assess cumulative environmental risks (e.g., childhood trauma, cannabis use). Collaborations: BRIDGE-S shares data with major consortia, including the Psychiatric Genomics Consortium (PGC) and EU-GEI, fostering cross-cultural and cross-disease insights. We further partnered with international groups in Vietnam, Nigeria and Greece to expand data collection efforts and scientific collaborations. Scientific Achievements: The study advances understanding of the genetic underpinnings of schizophrenia and gene-environment interactions through statistical models (e.g., Mendelian randomization, polygenic risk scores). Challenges: Self-reported clinical data requires validation against medical records. The recruitment of sensitive study populations requires a comprehensive set of recruitment strategy. Future Directions: BRIDGE-S plans to finalize statistical analyses, expand international collaborations to study disease trajectories, and inform precision medicine. In summary, BRIDGE-S has established a valuable resource for investigating SCZ etiology, providing data for genetic discoveries, enhanced risk and outcome prediction, and geneenvironment interactions. The project fosters global collaboration and sets a foundation for future translational research.
Publications
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S78SCHIZOPHRENIA GWAS OF YORUBAS IN SOUTHWESTERN NIGERIA. European Neuropsychopharmacology, 29, S153-S154.
Okewole, Adeniran; Oluwaranti, Oluwaseun; Adeniji, Adetayo; Awhangansi, Sewanu; Dade-Matthews, Adefunke; Awolaran, Dorcas; Sodiya, Olusegun; Daramola, Emmanuel; Dabiri, Idowu; Akingunola, Olumuyiwa; Owoeye, Isaiah; Omirin, Taiwo; Panagiotaropoulou, Georgia; Braun, Alice & Ripke, Stephan
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Increasing sample diversity in psychiatric genetics – Introducing a new cohort of patients with schizophrenia and controls from Vietnam – Results from a pilot study. The World Journal of Biological Psychiatry, 23(3), 219-227.
Nguyen, V. T.; Braun, A.; Kraft, J.; Ta, T. M. T.; Panagiotaropoulou, G. M.; Nguyen, V. P.; Nguyen, T. H.; Trubetskoy, V.; Le, C. T.; Le, T. T. H.; Pham, X. T.; Heuser-Collier, I.; Lam, N. H.; Böge, K.; Hahne, I. M.; Bajbouj, M.; Zierhut, M. M.; Hahn, E. & Ripke, S.
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Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature, 604(7906), 502-508.
Trubetskoy, Vassily; Pardiñas, Antonio F.; Qi, Ting; Panagiotaropoulou, Georgia; Awasthi, Swapnil; Bigdeli, Tim B.; Bryois, Julien; Chen, Chia-Yen; Dennison, Charlotte A.; Hall, Lynsey S.; Lam, Max; Watanabe, Kyoko; Frei, Oleksandr; Ge, Tian; Harwood, Janet C.; Koopmans, Frank; Magnusson, Sigurdur; Richards, Alexander L.; Sidorenko, Julia ... & van, Os Jim
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Study protocol of the Berlin Research Initiative for Diagnostics, Genetics and Environmental Factors in Schizophrenia (BRIDGE-S). BMC Psychiatry, 23(1).
Braun, Alice; Kraft, Julia & Ripke, Stephan
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Prioritizing causal genes in schizophrenia facilitates drug target discovery
Kraft J., Braun A., Awasthi S., Panagiotaropoulou G. M., Schipper M., Bell N., Posthuma D., Pardiñas A., Ripke S. & Heilbron K.
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Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies. Cell, 188(3), 640-652.e9.
Adams, Mark J.; Streit, Fabian; Meng, Xiangrui; Awasthi, Swapnil; Adey, Brett N.; Choi, Karmel W.; Chundru, V. Kartik; Coleman, Jonathan R.I.; Ferwerda, Bart; Foo, Jerome C.; Gerring, Zachary F.; Giannakopoulou, Olga; Gupta, Priya; Hall, Alisha S.M.; Harder, Arvid; Howard, David M.; Hübel, Christopher; Kwong, Alex S.F.; Levey, Daniel F. ... & McIntosh, Andrew M.
