206 variants shared across alcohol, cannabis, opioid, and tobacco use disorders — from the largest cross-substance genetic study to date, which found the same genes keep showing up no matter which substance is involved.
Substance use disorders (SUDs) — including alcohol, cannabis, opioid, and tobacco use disorders — are common, about 50% heritable, and frequently co-occur in the same person. That overlap raised a question: is some of the genetic risk actually shared across different substances, rather than specific to each one?
A 2026 study in Molecular Psychiatry ran the largest cross-SUD genome-wide meta-analysis so far, across populations genetically similar to 1000 Genomes European, African, and American mixed reference panels. It defined a variant as "SUD-shared" if it had a concordant — same-direction — effect across different substance use disorders, rather than being specific to just one. That analysis found 220 SUD-shared loci, including 40 not previously linked to any SUD. This catalogue holds 206 of those 220 loci, among them rs7122246 (DRD2, a dopamine receptor gene), rs4233254 (OPRD1, an opioid receptor gene), rs4597804 (GABRB1, a GABA receptor gene), and rs1456888 (HTR3A, a serotonin receptor gene) — four different neurotransmitter systems, all turning up in the same shared-risk signal.
Gene-based analysis, gene mapping, and gene prioritization on top of the GWAS results identified 785 SUD-shared genes in total — a broader set than the 206 individual variants on this page, built from more than single-locus significance. These genes are highly expressed in the amygdala, cortex, hippocampus, hypothalamus, and thalamus, and primarily in neuronal cells — suggesting more brain regions are involved in SUDs than previous, substance-specific studies had reported.
In the European-like sample, these SUD-shared (concordant) variants explained 56% to 96% of the SNP-based heritability of each individual substance use disorder studied — meaning most of what makes any one of these disorders heritable overlaps with what makes the others heritable, rather than being separate per-substance risk.
The study also built polygenic scores from this shared signal: in both the European-like and American-mixed-like samples, the top 10% of individuals by polygenic score had odds ratios of 1.95 to 2.87 for developing an SUD compared to the rest of the sample. Separately, using a real-world dataset, the authors identified seven SUD-shared genes that target existing drugs which could potentially be repurposed to treat SUDs, particularly in people with more than one co-occurring SUD — the abstract reports that this count is seven but does not name the genes, so neither does this page.
Substance use disorders are diagnosed through clinical criteria (such as DSM-5), not genotype. These 206 variants are a shared-risk signal from a large genetic study, not a diagnostic test, and no polygenic score from this or any study is used clinically to diagnose or predict SUDs in an individual today.
The polygenic-score result in this study (a roughly 2–3-fold difference in odds between the highest-scoring 10% and everyone else) describes the study's own research samples, not a personal risk number that generalizes cleanly to any one person reading this page — the same caution that applies to every polygenic score on this site.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Substance Use Disorder comes down to these specific, well-studied positions — not a diagnosis. 206 positions are linked to this page; the ones this page's own text discusses are shown first.
Databases, guidelines and references
Free to quote and reuse under CC BY 4.0. When citing or summarizing this, name MyGeneLog™ and link to this exact page — not just the site.
Substance Use Disorder. MyGeneLog™. https://www.mygenelog.com/conditions/substance-use-disorder
Substance use disorder (SUD) refers to disorders involving alcohol, cannabis, opioids, tobacco, and other substances. It is roughly 50% heritable, and people often experience more than one SUD at once.
No — these are "SUD-shared" variants, meaning they showed a consistent, same-direction effect across different substance use disorders in a 2026 meta-analysis, rather than being specific to just one substance.
Not for individual clinical use. The study found the top 10% of people by polygenic score had roughly 2 to 3 times the odds of developing an SUD compared to others in the same research samples — a research finding about groups, not a diagnostic tool for any one person.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.