Considerations for the application of polygenic scores to clinical care of individuals with substance use disorders

Abstract

Substance use disorders (SUDs) are highly prevalent and associated with excess morbidity, mortality, and economic costs. Thus, there is considerable interest in the early identification of individuals who may be more susceptible to developing SUDs and in improving personalized treatment decisions for those who have SUDs. SUDs are known to be influenced by both genetic and environmental factors. Polygenic scores (PGSs) provide a single measure of genetic liability that could be used as a biomarker in predicting disease development, progression, and treatment response. Although PGSs are rapidly being integrated into clinical practice, there is little information to guide clinicians in their responsible use and interpretation. In this Review, we discuss the potential benefits and pitfalls of the use of PGSs in the clinical care of SUDs, highlighting current research. We also provide suggestions for important considerations prior to implementing the clinical use of PGSs and recommend future directions for research.

Figure 1. Sample size and ancestry composition of the largest and/or most diverse GWAS of substance use/abuse phenotypes to date.

From left to right, bars represent Kember et al., 2023 (69); Zhou et al., 2023 (20); Saunders et al., 2022 (19); Koyanagi et al., 2024 (70); Kember et al., 2023 (69); Deak et al., 2022 (71); Johnson et al., 2020 (72); Pasman et al., 2018 (73); Kember et al., 2022 (24); Polimanti et al., 2020 (74); Toikumo et al., 2024 (22); Saunders et al., 2022 (19); Saunders et al., 2022 (19); Saunders et al., 2022 (19); and Saunders et al., 2022 (19). AUD, alcohol use disorder; AUDIT-C, Alcohol Use Disorders Identification Test–Consumption; CUD, cannabis use disorder; OUD, opioid use disorder; TUD, tobacco use disorder. EUR, European; EA, European American; AFR, African; AA, African American; AMR, admixed American; LA, Latin American; HA, Hispanic American; EAS, East Asian; SAS, South Asian.

Figure 2. Family-based and SNP-based heritability estimates and variance explained by polygenic scores for substance use disorders.

Absence of bars indicates that these data are not available for the corresponding ancestry group. Heritability estimates are on the liability scale. Family-based (h²) estimates are derived, from left to right, from Verhulst, Neale, and Kendler, 2015 (75); Verweij et al., 2010 (76); Tsuang et al., 1998 (77); and Do et al., 2015 (78). SNP-based (h2_SNP) estimates are derived, from left to right, from Zhou et al., 2023 (20); Zhou et al., 2023 (20); Zhou et al., 2023 (20); Levey et al., 2023 (79); Levey, et al., 2023 (79); Levey et al., 2023 (79); Deak et al., 2022 (21); Kember et al., 2022 (24); Toikumo et al., 2024 (22); Toikumo et al., 2024 (22); and Toikumo et al., 2024 (22). PRS polygenic scores (R²) estimates are derived, from left to right, from Zhou et al., 2023 (20); Johnson et al., 2020 (72); Deak et al., 2022 (21); and Toikumo et al., 2024 (22). AUD, alcohol use disorder; CUD, cannabis use disorder; OUD, opioid use disorder; TUD, tobacco use disorder; EUR, European; EA, European American; AFR, African; AA, African American; AMR, Admixed American; LA, Latin American; HA, Hispanic American.