Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study

Area of Science:

• Genetics and behavioral science
• Neuroscience
• Personalized medicine

Background:

• Addictive disorders arise from complex interactions between genetic, environmental, cultural, and social factors.
• Understanding the genetic underpinnings of substance use disorders (SUDs) is crucial for developing effective interventions.

Purpose of the Study:

• To assess the feasibility of whole-exome sequencing (WES) in family trios to identify genetic variants associated with severe SUDs.
• To explore potential genetic predispositions in individuals with severe alcohol use disorder (AUD), opioid use disorder (OUD), and nicotine dependence (ND).

Main Methods:

• Recruited family trios (subject and two family members) from a Singapore addiction service (2016-2018).
• Collected salivary samples for WES and analyzed genetic variants, focusing on individuals with severe AUD/OUD, nicotine dependence, and a family history of addiction.
• Captured demographic data and addiction severity.

Main Results:

• WES successfully identified genetic variants, including disruptive protein mutations, in all individuals.
• Discovered variants in genes previously linked to SUDs (e.g., PLEKHM3, CCSER1, LIMCH1, DNAH8) and TAS2R38 (bitterness perception).
• Feasibility study indicates a potential genetic predisposition in individuals with severe addiction profiles, polysubstance use, and family history.

Conclusions:

• Whole-exome sequencing of family trios is a feasible method for discovering genetic variants in SUDs.
• Findings support the hypothesis that genetic variants may predispose individuals to SUDs.
• This study provides a model for precision medicine approaches and personalized interventions for behavioral addictions and SUDs.