Evidence map›Paper›PMID 40162501›Full record

ArticlePsychological medicine2025

Polygenic overlap of substance use behaviors and disorders with externalizing and internalizing problems independent of genetic correlations.

Laila Al-Soufi, Guy Hindley, Linn Rødevand, Alexey A Shadrin, Piotr Jaholkowski, Vera Fominykh, Romain Icick, Markos Tesfaye, Javier Costas, Ole A Andreassen

Abstract read
In one paragraph

Article in Psychological medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
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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

10 authors.

Laila Al-SoufiPsychiatric Genetics group, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Galicia, Spain. Red de Investigación en Atención Primaria de Adicciones (RIAPAd).ORCID 0000-0003-2975-1636
Guy HindleyCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Linn RødevandCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Alexey A ShadrinCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Piotr JaholkowskiCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Vera FominykhCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Romain IcickCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Markos TesfayeCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Javier CostasPsychiatric Genetics group, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Galicia, Spain. Red de Investigación en Atención Primaria de Adicciones (RIAPAd).ORCID 0000-0003-0306-3990
Ole A AndreassenCentre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.ORCID 0000-0002-4461-3568

Funding

H2020 European Research Council 964874Helse Sør-Øst RHF 2022-073Ministerio de Universidades FPU18/03243Norges Forskningsråd 223273Stiftelsen Kristian Gerhard Jebsen SKGJ-MED-021
6 · The paper itself

Abstract

backgroundExternalizing and internalizing pathways may lead to the development of substance use behaviors (SUBs) and substance use disorders (SUDs), which are all heritable phenotypes. Genetic correlation studies have indicated differences in the genetic susceptibility between SUBs and SUDs. We investigated whether these substance use phenotypes are differently related to externalizing and internalizing problems at a genetic level.

methodsWe analyzed data from genome-wide association studies (GWAS) of four SUBs and SUDs, five externalizing traits, and five internalizing traits using the bivariate causal mixture model (MiXeR) to estimate genetic overlap beyond genetic correlation.

resultsTwo distinct patterns were found. SUBs demonstrated high genetic overlap but low genetic correlation of shared variants with internalizing traits, suggesting a pattern of mixed effect directions of shared genetic variants. Conversely, SUDs and externalizing traits exhibited considerable genetic overlap with moderate to high positive genetic correlation of shared variants, suggesting concordant effect direction of shared risk variants.

conclusionsThese results highlight the importance of the externalizing pathway in SUDs as well as the limited role of the internalizing pathway in SUBs. As MiXeR is not intended for the identification of specific genes, further studies are needed to reveal the underlying shared mechanisms of these traits.

Indexed as

Multifactorial InheritanceSubstance-Related DisordersAdultFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMalePhenotypealcohol consumptionalcoholismalcohol use disorderexternalizing problemsgenetic correlationinternalizing problemsnicotine dependencepolygenicitypsychiatric geneticsshared genetic susceptibilitytobacco use disorder

Identifiers

PMID40162501
PMCPMC12094651

What Socratic holds

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LicenceCC BY
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Registered trials

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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.