Polygenic risk score
Substance Use Disorder (general factor)
ICD-11 6C40 · Disorders due to substance use
The Substance Use Disorder polygenic risk score summarizes common-variant liability for the shared-addiction factor identified in recent PGC cross-substance analyses. SUD genetics spans alcohol, tobacco, cannabis, and other substance-use phenotypes.
The cross-substance addiction factor identified in recent PGC analyses captures shared genetic liability across alcohol, tobacco, cannabis, and opioid use disorders — a common-variant 'addiction axis' that transcends individual substances.
At a glance
The PGC substance use disorder GWAS captures shared genetic liability across alcohol, cannabis, opioid, and tobacco use disorders.
Substance Use Disorders include alcohol, cannabis, opioid, and tobacco addictions. Twin heritability ranges from 40% to 70% depending on the specific substance. The PGC Cross-Disorder 2025 multivariate analysis extracted a substance use factor (F5) from 11 psychiatric GWASes, which we score here as a general substance-use liability signal.
What the GWAS actually found
Substance-use-disorder GWAS have historically been substance-specific (AUDIT, cigarettes per day, cannabis use, etc.). Recent PGC Cross-Disorder-Group analyses have modeled a shared 'addiction factor' across substances, revealing common-variant architecture that transcends individual drug classes.
Twin-study heritability for substance-use disorders ranges roughly 0.40–0.70 depending on substance and age. Genetic overlap with ADHD, PTSD, MDD, and borderline personality disorder is well-documented — reflecting shared impulsivity, reward-sensitivity, and trauma-response biology.
Full citation: Psychiatric Genomics Consortium Cross-Disorder Working Group (2025). Multivariate GWAS of 11 psychiatric disorders identifies five latent liability factors; F5 is the substance-use factor.
How to read your percentile
Below 25th
Lower common-variant liability than most of the reference cohort. SUD risk is dominated by environmental exposures.
25th–75th
Typical range — near the population average. PRS is not clinically informative at this percentile.
Above 75th
Elevated common-variant liability. Age of first use, trauma exposure, and peer context matter more than genetics; early-intervention conversations with youth carry strong preventive evidence.
What this does not tell you
A cross-substance SUD PRS does not predict which substance an individual will use or become dependent on, nor does it distinguish dependence from casual or problematic use. Substance-specific PRS (alcohol, opioid, tobacco) capture partially distinct architectures.
Substance use is shaped by availability, peer context, age of first use, and cultural factors far more than any PRS. The score cannot predict treatment response or relapse. Environmental risk factors — trauma exposure, early-onset use, social context — dominate genetic risk in most individual trajectories.
Related traits
Substance Use Disorder (general factor) shares common-variant architecture with several other psychiatric conditions. Genetic correlations (rg) reflect how often the same variants move risk for both traits in the same direction.
Frequently asked questions
Does this score predict addiction?
No. The PRS is a probabilistic population-level signal. Substance-use trajectories depend heavily on environment, availability, and social context. A high PRS modestly elevates risk conditional on exposure but does not predict individual outcomes.
Does it predict which substance I'll have trouble with?
Not cleanly. The cross-substance factor captures shared liability across substances. Substance-specific PRS (alcohol, opioid, tobacco, cannabis) are partially distinct but smaller and less well-validated.
Why do ADHD and SUD share so much genetic architecture?
Shared traits like impulsivity, reward-sensitivity, and difficulty with delayed gratification have common-variant underpinnings that load onto both ADHD and SUD. This is why untreated ADHD is a recognized risk factor for SUD onset.
Should I avoid all substances if my PRS is elevated?
That's a personal decision best discussed with a clinician, not prescribed by this report. Elevated PRS is one of many risk inputs; age of first use and total exposure are more important modifiable factors. If you have SUD in your family, early conversations about substance use in adolescence have strong preventive evidence.
Sources
- PGC Substance Use Disorders Working Group. pgc.unc.edu/for-researchers/working-groups/substance-use-disorders-workgroup/
Note: This trait references a recent or pre-publication GWAS. Specific cohort numbers, loci counts, and variance-explained estimates on this page will be refined when the final peer-reviewed source is published. The product uses summary statistics from the source cited above.
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