Evidence mapPaperPMID 42016913Full record

ArticleGeneral psychiatry2026

Shared genetic variants across substance use disorders implicate common neurobiological pathways, a genome-wide mixed methods study.

Børge Holen, Zillur Rahman, Alexey A Shadrin, Romain Icick, Kevin S O'Connell, Linn Rødevand, Nadine Parker, Markos Tesfaye, Piotr Jaholkowski, Oleksandr Frei and 4 more

Abstract read
In one paragraph

Article in General psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Børge HolenCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Zillur RahmanCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Alexey A ShadrinCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Romain IcickCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Kevin S O'ConnellCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Linn RødevandCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Nadine ParkerCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Markos TesfayeCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Piotr JaholkowskiCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Oleksandr FreiCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Anders M DaleDepartment of Radiology University of California, San Diego La Jolla California USA.
Srdjan DjurovicCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Ole A AndreassenCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.
Olav B SmelandCentre for Precision Psychiatry Institute of Clinical Medicine University of Oslo Oslo Norway.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Substance use disorders (SUDs) are highly heritable, but the extent of shared and distinct genetic architecture across different SUDs is unclear. Aims: To compare the genetic architectures of alcohol use disorder (AUD), cannabis use disorder (CUD) and opioid use disorder (OUD) and to identify shared and unique genetic loci. Methods: We analysed large-scale genome-wide association study (GWAS) summary statistics from individuals of European ancestry recruited in Europe and the USA. The mixture model MiXeR was used to estimate the unique genetic architecture characteristics of each SUD, including its polygenicity, single nucleotide polymorphism (SNP)-heritability and discoverability, a measure of the distribution of genetic signal across all causal variants. Pairwise conditional/conjunctional false discovery rate (cond/conjFDR) analyses identified shared loci, followed by biological annotation of implicated genes. Results: AUD demonstrated the highest polygenicity, followed by CUD and OUD. SNP-based heritability was 0.10 for AUD and OUD and 0.01 for CUD. Discoverability was highest for OUD, followed by AUD and CUD. Currently, genome-wide significant SNPs explain 2.0% of AUD, 0.3% of CUD and 0.2% of OUD variance. Cond/conjFDR identified 39 novel loci for AUD, 10 for CUD and 1 for OUD. Of implicated genes, most were expressed in the brain, including several involved in gamma-aminobutyric acid and dopaminergic neurotransmission, opioid neurophysiology, myelination, DNA recombination, apoptosis and ubiquitin-dependent protein catabolism. Conclusions: SUDs have polygenic architectures with many shared loci and are similar with regards to some characteristics. However, the level of polygenicity differs across SUDs, with AUD being considerably more polygenic than OUD, whereas CUD is intermediate in terms of its polygenicity. The novel loci implicate genes primarily expressed in the brain, involving a variety of biological functions. The findings expand our view of the aetiology of these disorders, while supporting the hypothesis of a shared set of pleiotropic SUD genes.

Indexed as

alcohol use disordercannabis use disordercommon neurobiological pathwaysgenetic architecturenovel substance use disorder genetic lociopioid use disordershared geneticssubstance use disorder

Identifiers

PMID42016913
PMCPMC13095382

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.