Multiple substance use disorders may share inherited genetic signature

March 24, 2023
Findings could lead to universal therapies for alcohol, tobacco, cannabis, opioid addictions.

A new study suggests that a common genetic signature may increase a person’s risk of developing substance use disorders, regardless of whether the addiction is to alcohol, tobacco, cannabis or opioids. The research, led by Washington University School of Medicine in St. Louis, eventually could lead to universal therapies to treat multiple substance use disorders and potentially help people diagnosed with more than one.

Published March 22 in the journal Nature Mental Health, the study’s findings are drawn from an analysis of genomic data from more than 1.1 million people of mostly European ancestry and a smaller population of people of African ancestry.

As part of the study, the researchers compiled a list of approved and investigational pharmaceutical drugs that have the potential to be repurposed to treat substance use disorders because the drugs may target the effects of the newly discovered genetic signature associated with addiction. The list includes more than 100 drugs to investigate in future clinical trials, including those that can influence regulation of dopamine signaling.

The risk of developing substance use disorders is influenced by the complex interplay of genetics and environment. The investigators looked for variations in the genome that were closely associated with such disorders in many individuals across large sample sizes, including 1,025,550 people of European ancestry and 92,630 people of African ancestry. This type of genome-wide association study can identify key genetic variations that are associated with increased risk of having one or multiple disorders.

The team found that the genetic variation underlying addiction includes 19 single letter differences in the DNA code that were significantly associated with general addiction risk, which could inform development of universal therapies for multiple addictions. It also includes 47 genetic variants linked to specific substance disorders — nine for alcohol, 32 for tobacco, five for cannabis and one for opioids. Such information could point to novel treatments for addiction to individual substances. However, it is likely that many more genetic differences are actually involved in shaping a person’s genetic liability to one or more addictions.

WUSTL release