Home›Genetics & Precision Medicine› 19 genome-wide significant loci identify genetic architecture and high correlations with other substance use disorders
19 genome-wide significant loci identify genetic architecture and high correlations with other substance use disordersGenes linked to stimulant addiction found in largest study yet
medRxivPublished June 11, 2026Study authors: Beck, S. E.; Deak, J. D.; Levey, D. F.; Ge, T.; Jeffries, P. W.; Lai, D.; Mallard, T. T.; Degenhardt…DOI ↗Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development
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Key Takeaway
Note the strong genetic overlap between stimulant, cannabis, and opioid use disorders as evidenced by high correlation coefficients.
This meta-analysis investigates the genetic architecture of Stimulant Use Disorder using a large multi-ancestry sample of 709,369 individuals. The study identifies 19 total genome-wide significant loci associated with the disorder, including specific markers such as DRD2*rs5794864 in European populations and CHRNA5*rs55781567 across multi-ancestry groups.
Key findings include significant genetic correlations with other substance use disorders: a correlation of rg=0.94 with cannabis use disorder and rg=1.01 with opioid use disorder. Additionally, polygenic risk scores showed positive associations with Stimulant Use Disorder in both European (OR=3.28) and Admixed American (OR=2.01) hold-out samples.
The authors note that while the study provides high statistical power due to the large sample size, genetic correlations do not imply direct causation. Polygenic risk scores are intended as predictive tools rather than diagnostic certainties. These findings provide a foundation for understanding the shared biological pathways between stimulant, cannabis, and opioid use disorders.
How this fits prior evidence
This meta-analysis extends existing knowledge of the genetic architecture of substance use disorders by identifying 19 genome-wide significant loci for Stimulant Use Disorder. It specifically addresses gaps in multi-ancestry data and quantifies the high genetic correlation (rg=0.94) with cannabis use disorder and (rg=1.01) with opioid use disorder, providing a genetic context to the risks associated with cannabis and opioid use mentioned in prior coverage.
Why do some people who try stimulants like cocaine or methamphetamine get hooked while others don't? A massive new study suggests part of the answer lies in our DNA.
Researchers analyzed genetic data from over 700,000 people, including nearly 34,000 with stimulant use disorder. They found 19 specific regions in the genome that are linked to the condition. One of these regions, in a gene called FTO, was only seen in men. FTO is already known for its role in obesity, which hints at a surprising connection between addiction and metabolism.
The study also revealed that the genetic risk for stimulant addiction is very similar to the risk for cannabis and opioid use disorders. In fact, the genetic overlap was nearly complete. This suggests that some people may have a general genetic vulnerability to substance use disorders, not just one type of drug.
It's important to note that this is a genetic association study, not a cause-and-effect experiment. The findings don't mean that having these genes guarantees addiction. But they do point to biological pathways that could be targets for future treatments. The large sample size gives the results strong statistical power, making them more reliable than previous smaller studies.
What this means for you:
Stimulant addiction has a strong genetic component, with 19 risk regions identified.
Common questions
What is stimulant use disorder?
Stimulant use disorder is a condition where a person has a problematic pattern of using stimulant drugs like cocaine, methamphetamine, or prescription stimulants. It can lead to health issues, trouble at work or school, and difficulty controlling use. This study looked at the genetic factors that may increase risk.
How many people were in this study?
The study included 709,369 people total. Among them, 33,977 had stimulant use disorder and 675,392 were controls (people without the disorder). This large sample size gives the results strong statistical power.
What does a genetic correlation of 0.94 mean?
A genetic correlation of 0.94 between stimulant use disorder and cannabis use disorder means that the genetic factors influencing these two conditions are very similar. A value of 1.0 would mean they are identical. This suggests a shared genetic vulnerability to different substance use disorders.
Does this study prove that genes cause addiction?
No. The study found associations between certain genetic regions and stimulant use disorder, but it does not prove that these genes directly cause addiction. The researchers used a method called Mendelian randomization to explore relationships, but the primary findings are associations, not causal links.
Stimulant use disorder (StimUD) is a significant public health problem, but genetic studies have been limited by small sample sizes. We conducted genome-wide association studies (GWAS) of StimUD in the Million Veteran Program (MVP) and All of Us (AOU), followed by meta-analysis with FinnGen and 10 additional datasets, for a total of 709,369 individuals (Ncases=33,977, Ncontrols=675,392) in four broad ancestry groups: European (EUR) (Ncases=22,564, Ncontrols=624,672), African (AFR) (Ncases=7,574, Ncontrols=34,189), Admixed American (AMR) (Ncases=3,657, Ncontrols=15,698), and East Asian (EAS) (Ncases=182, Ncontrols=833). Population-specific SNP heritability was 6.1% in EUR and 2.4% in AFR. We discovered a total of 19 genome-wide-significant loci, six in EUR, including DRD2*rs5794864, P=7.32E-10, one in AFR, five in a multi-ancestry meta-analysis, including CHRNA5*rs55781567, P=3.27E-9, two in a male-only meta-analysis, including FTO*rs8057044, P=9.50E10-9, and five in a meta-analysis of sex-stratified results. In a hold-out AOU subsample (NEUR=18,841, NAFR=12,263, NAMR=9,739), ancestry-specific polygenic risk scores were significantly associated with StimUD in EUR (OR=3.28, 95% confidence interval (CI)=2.89-3.71) and AMR (OR=2.01, 95% CI=1.71-2.37). Transcriptome-wide association studies, fine-mapping, and colocalization analyses prioritized additional genes (e.g., GPX1, BSN). Genetic correlation, Mendelian randomization, and causal mixture analyses revealed relationships with other substance use and use disorder phenotypes, including cannabis use disorder (rg=0.94, P=5.43E-237) and opioid use disorder (rg=1.01, P=4.40E-107), and other psychiatric traits, including anxiety, depression, neuroticism, and attention-deficit/hyperactivity disorder. This is the first well-powered GWAS of StimUD, and it offers significant insights into disease biology.
