Predictive performance for alcohol use disorder of polygenic scores based on the general addiction risk factor and problematic alcohol use.

Abstract

Polygenic scores (PGSs) may play a role in targeted prevention of alcohol use disorder (AUD) by risk stratification. A latent genetic factor representing common liability to different substance use disorders (SUDs), known as the addiction risk factor (AdRF), was recently characterized. Our aim was to analyze the predictive performance for AUD of the AdRF PGS, comparing it with PGSs of problematic alcohol use (PAU) and of a common liability factor to substance use involvement. PGSs were estimated across two datasets, comprising 1637 treatment-seeking AUD patients and 4178 controls. Logistic regression was used to evaluate performance of ancestry-normalized PGSs. Subgroup sensitivity analyses were tested based on clinical data. Sex-dependent effects were assessed by comparing PGSs between sexes. Tail-based measures revealed a better performance of the AdRF PGS than the other PGSs. Compared with the remaining subjects, those at the top decile of PGS presented a 3.3-fold greater odds of AUD. Other analyses revealed similar performance of the AdRF and PAU PGSs. The effect estimates were larger in subgroups with addictive and psychiatric comorbidities, higher severity, and earlier age of onset. Women patients presented higher PAU and AdRF PGSs than men patients. This new generation of PGSs is one step closer to precision public health for AUD prevention. Alcohol-specific genetic factors are not determinant for predicting AUD risk, which may benefit from shared genetic susceptibility among different SUDs. Our data suggest sex differences in genetic susceptibility, probably as a result of complex interplay between genes and social environment.