Citation

Nurnberger JIJ, Wang Y, Zang Y, Lai D, Wetherill L, Edenberg HJ, Aliev F, Plawecki MH, Chorlian D, Chan G, Bucholz K, Bauer L, Kamarajan C, Salvatore JE, Kapoor M, Hesselbrock V, Dick D, Bierut L, McCutcheon V, Meyers JL, Porjesz B, Kramer J, Kuperman S, Kinreich S, Anokhin AP. Biol. Psychiatry Glob. Open Sci. 2022; 2(4): 379-388.

Copyright

(Copyright © 2022, Elsevier Publishing)

DOI

10.1016/j.bpsgos.2021.10.007

PMID

36324664

PMCID

PMC9616304

Abstract

BACKGROUND: Genome-wide association studies have been conducted in alcohol use disorder (AUD), and they permit the use of polygenic risk scores (PRSs), in combination with clinical variables, to predict the onset of AUD in vulnerable populations.

METHODS: A total of 2794 adolescent/young adult subjects from the Collaborative Study on the Genetics of Alcoholism were followed, with clinical assessments every 2 years. Subjects were genotyped using a genome-wide chip. Separate PRS analyses were performed for subjects of European ancestry and African ancestry. Age of onset of DSM-5 AUD was evaluated using the Cox proportional hazard model. Predictive power was assessed using receiver operating characteristic curves and by analysis of the distribution of PRS.

RESULTS: European ancestry subjects with higher than median PRSs were at greater risk for onset of AUD than subjects with lower than median PRSs (p = 3 × 10(-7)). Area under the curve for the receiver operating characteristic analysis peaked at 0.88 to 0.95 using PRS plus sex, family history, comorbid disorders, age at first drink, and peer drinking; predictive power was primarily driven by clinical variables. In this high-risk sample, European ancestry subjects with a PRS score in the highest quartile showed a 72% risk for developing AUD and a 35% risk of developing severe AUD (compared with risks of 54% and 16%, respectively, in the lowest quartile).

CONCLUSIONS: Predictive power for PRSs in the extremes of the distribution suggests that these may have future clinical utility. Uncertainties in interpretation at the individual level still preclude current application.

Language: en

Keywords

Survival analysis; Alcohol use disorder; Clinical variables; Polygenic risk scores; Prediction of illness; Receiver operating characteristics curves