Genetic Variants May Enhance Predictions for Alcohol Addiction Treatment Efficacy

Recent research has unveiled that multiple genetic variants could play a significant role in determining the effectiveness of a medication used for treating alcohol use disorder (AUD). This discovery highlights the potential for personalized treatment strategies based on genetic profiling.

Alcohol use disorder remains a prevalent issue, yet only a small fraction of affected individuals receive medication, with just 2% prescribed treatment in 2022. Among the medications available, topiramate has shown promise in off-label applications, demonstrating its ability to decrease the frequency of heavy drinking and mitigate related issues.

A collaborative research effort involving experts from the University of Pennsylvania and Yale explored whether specific genetic variants associated with AUD could influence the therapeutic outcomes of topiramate. Previous investigations indicated a potential link with a single genetic variant; however, later studies did not corroborate its moderating effects on treatment results.

The current study, published in Alcohol: Clinical and Experimental Research, aimed to assess whether a broader assessment of genetic risk, through polygenic scores, could better predict the medication's efficacy. Polygenic scores aggregate the influence of numerous genetic variants linked to AUD, and they have been previously utilized to identify individuals at risk for substance use disorders.

Data from 285 patients of European descent diagnosed with AUD, who were treated with either topiramate or a placebo, formed the basis of this analysis. All participants underwent genetic testing to inform the study's findings.

To construct the polygenic scores, researchers utilized existing large genetic databases of individuals with European ancestry to compile information on multiple genetic variants associated with four alcohol-related traits: problematic alcohol use (PAU), overall alcohol consumption (DPW), time to relapse following treatment (TR), and the duration until a return to heavy drinking (THR).

Through statistical analysis, the research team examined the correlation between these genetic risk measures and the effectiveness of topiramate in reducing heavy drinking and associated problems. Results indicated that topiramate significantly outperformed the placebo in reducing both alcohol-related issues and heavy drinking days.

Moreover, the treatment's impact on alcohol-related problems was noticeably linked to three specific polygenic scores (PAU, TR, and THR). Those patients exhibiting higher polygenic scores demonstrated a more pronounced response to topiramate, experiencing greater reductions in alcohol-related problems compared to those with lower genetic risk profiles.

This study reinforces the notion that genetic predisposition can influence the effectiveness of medications for AUD. It suggests that polygenic scores may serve as a valuable tool for tailoring treatments to individual patients, thereby enhancing the likelihood of successful outcomes. The complexity of treatment responses, shaped by numerous genetic variants, underscores the potential utility of polygenic scores in understanding the interplay between genetics and medication efficacy in AUD.

For further reading and detailed findings, the original study can be referenced: Moderation of treatment outcomes by polygenic risk for alcohol-related traits in placebo-controlled trials of topiramate, Alcohol, Clinical and Experimental Research (2025).