ArticlemedRxiv : the preprint server for health sciences2025
Towards Scalable Biomarker Discovery in Posttraumatic Stress Disorder: Triangulating Genomic and Phenotypic Evidence from a Health System Biobank.
Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Importance: Biomarkers can potentially improve the diagnosis, monitoring, and treatment of posttraumatic stress disorder (PTSD). However, PTSD biomarkers that are scalable and easily integrated into real-world clinical settings have not been identified. Objective: To triangulate phenotypic and genomic evidence from a health system biobank with a goal of identifying scalable and clinically relevant biomarkers for PTSD. Design setting and participants: The analysis was conducted between June to November 2024 using genomic samples and laboratory test results recorded in the Mass General Brigham (MGB) Health System. The analysis included 23,743 European ancestry participants from the nested MGB Biobank study. Exposures: The first exposure was polygenic risk score (PRS) for PTSD, calculated using the largest available European ancestry genome-wide association study (GWAS), employing a Bayesian polygenic scoring method. The second exposure was a clinical diagnosis of PTSD, determined by the presence of two or more qualifying PTSD phecodes in the longitudinal electronic health records (EHR). Main outcomes and measures: The primary outcomes were the inverse normal quantile transformed, median lab values of 241 laboratory traits with non-zero Results: Sixteen unique laboratory traits across the cardiometabolic, hematologic, hepatic, and immune systems were implicated in both genomic and phenotypic lab-wide association scans (LabWAS). Two-sample Mendelian randomization analyses provided evidence of potential unidirectional causal effects of PTSD liability on five laboratory traits. Conclusion and relevance: These findings demonstrate the potential of a triangulation approach to uncover scalable and clinically relevant biomarkers for PTSD.
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