Polygenic risk factors for comorbid diagnoses in individuals with substance use disorders: A phenome-wide survival analysis
Year: 2026
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Persons with substance use disorders (SUD) often suffer from additional comorbidities. Researchers have explored this overlap via phenome-wide association studies (PheWASs). However, PheWASs are largely cross-sectional, limiting our understanding of whether diagnoses predate the development of an SUD. We characterize whether polygenic scores (PGSs) are associated with time to comorbid diagnoses in electronic health records (EHR) after the first documented SUD diagnosis. METHODS: = 21,357), whether PGS for alcohol use disorders, cannabis use disorders, depression, externalizing, posttraumatic stress disorder, and schizophrenia were associated with subsequent diagnoses via a phenome-wide survival analysis. RESULTS: Multiple SDoHs were associated with lifetime SUD diagnosis, with annual household income having the largest overall associations (e.g. <$10 K annually vs $100 K-$150 K annually: OR = 4.18; 95% CI = 3.92, 4.45). There were 86 phenome-wide significant PGS associations with subsequent diagnoses across various bodily systems. PGSs for alcohol use disorders, posttraumatic stress disorder, and schizophrenia were each associated with time to their respective diagnoses. CONCLUSIONS: Social determinants, especially those related to income, have profound associations with lifetime SUD risk. Additionally, PGSs for psychiatric conditions are associated with multiple post-SUD diagnoses within those with a SUD, suggesting PGS may capture information beyond lifetime risk, including timing and severity of comorbidities related to SUD.
Source: Psychological Medicine
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,550
Awards: Illinois Precision Medicine Consortium , Healthy Americas: All of Us Research Program, G1969433312, G2187930703, Empowerment-focused Outreach, Education and Enrollment of Tennessee Older Adults in the All of Us Research Program through Community Efforts by FiftyForward, Research Matters: Creating Possibilities to Achieve Health and Wellness for All of Us Research Program, Precision Medicine Initiative Cohort Program Biobank, Communications Design and Development for NIH Precision Medicine Initiative Research Projects, New York City Consortium for Precision Medicine, Technology to Empower Changes in Health (TECH) Network Participant Technologies Center, University of Arizona-Banner Health All of Us Research Program , The New England Precision Medicine Consortium of the All of Us Research Program, All of Us Wisconsin , Data and Research Support Center , All of Us Pennsylvania, Trans-America Consortium of the Health Care Systems Research Network for the All of Us Research Program, Research Center in Minority Institutions (RCMI) at City College, Southern All of Us Network, SouthEast Enrollment Center (SEEC) , Adaptive Platform for Personalized Engagement, G8355735039, California Precision Medicine Research Program Consortium, Communication Implementation and Coordination for NIH Precision Medicine Initiative Research Projects, Using the Genetic Architecture of Substance Use Disorders to Advance Gene Identification and Understanding of Pathways of Risk, Genetic Comorbidity of PTSD and Substance Use Disorders in Diverse Populations., Genetic relationships between PTSD and Alcohol Use Disorder: Integrating GWAS and Deeply Phenotyped Longitudinal data., Cross-Population Working Group on Genes and Environment in Major Depression (POP-GEM): Advancing the Understating of Etiology through Diversity, PRIDEnet for the All of Us Research Program
OpenAlex ID: W7163056534