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Hartwell EE, Merikangas AK, Verma SS, et al. Genetic liability for substance use associated with medical comorbidities in electronic health records of African- and European-ancestry individuals. Addict Biol. 2021;e13099doi: 10.1111/adb.13099.
Hartwell, E. E., Merikangas, A. K., Verma, S. S., Ritchie, M. D., Kranzler, H. R., & Kember, R. L. (2021). Genetic liability for substance use associated with medical comorbidities in electronic health records of African- and European-ancestry individuals. Addiction biology, e13099. https://doi.org/10.1111/adb.13099
Hartwell, Emily E, et al. "Genetic liability for substance use associated with medical comorbidities in electronic health records of African- and European-ancestry individuals." Addiction biology vol. (2021): e13099. doi: https://doi.org/10.1111/adb.13099
Hartwell EE, Merikangas AK, Verma SS, Ritchie MD, Kranzler HR, Kember RL. Genetic liability for substance use associated with medical comorbidities in electronic health records of African- and European-ancestry individuals. Addict Biol. 2021 Oct 05;e13099. doi: 10.1111/adb.13099. Epub 2021 Oct 05. PMID: 34611967.
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Addict Biol. 2021 Oct 05;e13099. doi: 10.1111/adb.13099. Epub 2021 Oct 05.

Genetic liability for substance use associated with medical comorbidities in electronic health records of African- and European-ancestry individuals.

Addiction biology

Emily E Hartwell, Alison K Merikangas, Shefali S Verma, Marylyn D Ritchie, Henry R Kranzler, Rachel L Kember

Affiliations

  1. Mental Illness Research, Education and Clinical Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.
  2. Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  3. Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  4. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  5. Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  6. Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

PMID: 34611967 DOI: 10.1111/adb.13099

Abstract

Polygenic risk scores (PRS) represent an individual's summed genetic risk for a trait and can serve as biomarkers for disease. Less is known about the utility of PRS as a means to quantify genetic risk for substance use disorders (SUDs) than for many other traits. Nonetheless, the growth of large, electronic health record-based biobanks makes it possible to evaluate the association of SUD PRS with other traits. We calculated PRS for smoking initiation, alcohol use disorder (AUD), and opioid use disorder (OUD) using summary statistics from the Million Veteran Program sample. We then tested the association of each PRS with its primary phenotype in the Penn Medicine BioBank (PMBB) using all available genotyped participants of African or European ancestry (AFR and EUR, respectively) (N = 18,612). Finally, we conducted phenome-wide association analyses (PheWAS) separately by ancestry and sex to test for associations across disease categories. Tobacco use disorder was the most common SUD in the PMBB, followed by AUD and OUD, consistent with the population prevalence of these disorders. All PRS were associated with their primary phenotype in both ancestry groups. PheWAS results yielded cross-trait associations across multiple domains, including psychiatric disorders and medical conditions. SUD PRS were associated with their primary phenotypes; however, they are not yet predictive enough to be useful diagnostically. The cross-trait associations of the SUD PRS are indicative of a broader genetic liability. Future work should extend findings to additional population groups and for other substances of abuse.

© 2021 Society for the Study of Addiction.

Keywords: electronic health record; genome-wide association study; phenome-wide association study; polygenic risk score; substance use disorders

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