Social and Polygenic Risk Factors for Time to Comorbid Diagnoses in Individuals with Substance Use Disorders: A Phenome-Wide Survival Analysis.

Importance: Persons with substance use disorders (SUD) often suffer from additional comorbidities, including psychiatric conditions and physical health problems. Researchers have explored this overlap in electronic health records (EHR) using phenome wide association studies (PheWAS) to characterize how different indicators are related to all conditions in an individual's EHR. However, analyses have been largely cross-sectional in nature.

Objective: To characterize whether various social and genetic risk factors are associated with time to comorbid diagnoses in electronic health records (EHR) after the first diagnosis of SUD.

Design: Leveraging those with EHR and whole-genome sequencing data in All of Us (N = 287,012), we explored whether social determinants of health are associated with lifetime risk of SUD. Next, within those with a diagnosed SUD (N = 17,460), we examined whether polygenic scores (PGS) were associated with time to comorbid diagnoses performing a phenome-wide survival analysis.

Setting: Participating health care organizations across the United States.

Participants: Participants in the All of Us Research Program with available EHR and genomic data.

Exposures: Social determinants of health and polygenic scores (PGS) for psychiatric and substance use disorders.

Main Outcomes And Measures: Phecodes for diagnoses derived from International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification, codes from EHR.

Results: Multiple social and demographic risk factors were associated with lifetime SUD diagnosis. Most strikingly, those reporting an annual income <$10K had 4.5 times the odds of having an SUD diagnosis compared to those reporting $100-$150K annually (OR = 4.48, 95% CI = 4.01, 5.01). PGSs for alcohol use disorders, schizophrenia, and post-traumatic stress disorder were associated with time to their respective diagnoses (HR = 1.10, 95% CI = 1.06, 1.14; HR = 1.13, 95% CI = 1.06, 1.20; HR = 1.15, 95% CI = 1.08, 1.22). A PGS for ever-smoking was associated with time to subsequent smoking related comorbidities and additional SUD diagnoses HR = 1.6 to 1.16).

Conclusions And Relevance: Social determinants, especially those related to income have profound associations with lifetime SUD risk. Additionally, PGS may include information related to outcomes above and beyond lifetime risk, including timing and severity.