On Mar. 20, 2026, researchers of a Rutgers Health–led study led by Holly Poore, a faculty instructor of psychiatry at Rutgers Robert Wood Johnson Medical School, announced analyzed genetic data from previously published genome-wide association studies totaling more than 2.2 million individuals to understand how genes shape vulnerability to alcohol, tobacco, cannabis and opioid use disorders. 

According to the study published in Nature Mental Health, members of the team found genetic risk operates along two main pathways:

• A broad “behavioral disinhibition” or externalizing pathway, which involves brain systems for reward processing, self-control and risk-taking. Externalizing refers to a heritable pattern of behaviors characterized by difficulty regulating impulses and actions such as impulsivity, attention-deficit/hyperactivity disorder (ADHD), conduct problems and risk-taking behaviors. This pathway cuts across many forms of addiction and related behavioral outcomes.
• Substance-specific pathways that are more narrowly tied to particular drugs (for example, genes involved in alcohol metabolism or nicotine receptors).

“Most of the genetic predisposition to substance use disorders isn’t about how bodies respond to drugs; it’s about how brains are wired,” said Danielle Dick, director of the Rutgers Addiction Research Center within the Rutgers Brain Health Institute and senior author of the study. “Specifically, risk is mostly related to genes that broadly impact how our brains process rewards and regulate behavior.” 

Dick added, “Those same genes show up across many outcomes – things like ADHD, conduct problems and other risky behaviors – and then layered on top of that are genes that are more specific to each substance. What this paper does, for the first time, is tease apart those pathways at the genomic level.”

Using advanced genomic methods, the researchers analyzed four substance use disorders – alcohol, tobacco, cannabis and opioids – together with related externalizing traits such as ADHD, risk-taking and initiation of substance use. This approach allowed them to identify hundreds of genetic variants associated with a broad externalizing liability as well as genes that were more specific to particular substances.

The researchers found that modeling addiction together with these other traits greatly increased their ability to detect genetic effects without sacrificing the means to see substance-specific signals. Many of the genes linked to the broad liability were involved in brain signaling, reward processing and neural plasticity, while substance-specific genes mapped onto pathways such as alcohol metabolism or nicotinic acetylcholine receptors implicated in tobacco use.