Evidence map›Paper›PMID 41152253›Full record

ArticleThe American journal of psychiatry2026

Characterizing the Pleiotropic Architecture of Impulsivity and Its Links to Psychopathology and Neurodevelopment.

Travis T Mallard, Justin D Tubbs, Mariela Jennings, Yingzhe Zhang, Daniel E Gustavson, Andrew D Grotzinger, Margaret L Westwater, Camille M Williams, Rebecca G Fortgang, Sarah L Elson and 9 more

Abstract read
In one paragraph

Article in The American journal of 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

19 authors.

Travis T MallardCenter for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston.ORCID 0000-0002-3265-3001
Justin D TubbsPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston.
Mariela JenningsDepartment of Psychiatry, University of California San Diego, La Jolla.
Yingzhe ZhangDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston.
Daniel E GustavsonInstitute for Behavioral Genetics, University of Colorado Boulder.
Andrew D GrotzingerInstitute for Behavioral Genetics, University of Colorado Boulder.
Margaret L WestwaterDepartment of Psychiatry, University of Oxford, Oxford, UK.
Camille M WilliamsPopulation Research Center, University of Texas at Austin.
Rebecca G FortgangDepartment of Psychiatry, Harvard Medical School, Boston.
Sarah L Elson23andMe, Inc., Sunnyvale, CA.
Pierre Fontanillas23andMe, Inc., Sunnyvale, CA.
Lea K DavisDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Armin RaznahanSection on Developmental Neurogenomics, NIMH, Bethesda, MD.
Elliot M Tucker-DrobPopulation Research Center, University of Texas at Austin.
Karmel W ChoiPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston.
Tian GePsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston.
Jordan W SmollerCenter for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston.
Abraham A PalmerDepartment of Psychiatry, University of California San Diego, La Jolla.
Sandra Sanchez-RoigeDepartment of Psychiatry, University of California San Diego, La Jolla.ORCID 0000-0001-6137-5699

Funding

Section on Developmental NeurogenomicsZIAMH002949 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI RAZNAHAN, ARMIN · 2016 to 2025
$30.0M
Dissecting the Multivariate Genetic Architecture of Psychiatric DiseasesR01MH120219 · NIMH · UNIVERSITY OF TEXAS AT AUSTIN · PI NIVARD, MICHEL GUILLAUME, TUCKER-DROB, ELLIOT MAX · 2020 to 2024
$3.3M
Partners Healthcare Training Program in Precision and Genomic MedicineT32HG010464 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI HEIDI L REHM, JORDAN W SMOLLER · 2019 to 2026
$3.1M
Building Bridges to Allow Cross-species Translational genetics for the Study of AddictionDP1DA054394 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SANCHEZ ROIGE, SANDRA · 2021 to 2025
$2.4M
Digital Monitoring of Impulsivity as a Proximal Risk Factor for Suicidal OutcomesK23MH132766 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI Rebecca Gwen Fortgang · 2023 to 2026
$783k
Understanding developmental neurogenomic mechanisms in externalizing disordersK08MH135343 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI Travis T Mallard · 2024 to 2026
$588k
Intramural NIH HHS ZIA MH002949NHGRI NIH HHS T32 HG010464NIDA NIH HHS DP1 DA054394NIMH NIH HHS K08 MH135343NIMH NIH HHS K23 MH132766NIMH NIH HHS R01 MH120219
6 · The paper itself

Abstract

objectiveImpulsivity is a complex mental construct and a core feature of many psychiatric and neurological conditions. The aim of this study was to formally model the genetic architecture of eight impulsive traits, identifying their shared and distinct genetic influences, to advance our biological understanding of impulsivity.

methodsThe authors analyzed genetic data from up to 133,517 individuals using novel multivariate genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) approaches. Bioinformatic analyses were conducted to identify gene expression patterns and neurobiological correlates, and polygenic score analyses were used to examine the ways in which genetic liability for impulsivity relates to clinical outcomes.

resultsThe analyses revealed pervasive pleiotropy that largely counters theories of impulsivity as a unitary construct. GWAS and TWAS analyses identified 18 loci and 93 genes, respectively, that have diverse effects on self-regulation, including a hotspot at 17q21.31 that harbors genes involved in neurodevelopmental and neurodegenerative disorders. Bioinformatic analyses revealed that many biological correlates have divergent effects on impulsive traits, including upregulated gene expression during early neurodevelopment and altered cortical morphometry of the inferior frontal gyrus in adulthood. Polygenic score analyses suggest that liability for impulsivity may canalize across development, as polygenic influences on clinical outcomes tended to operate via shared pathways early in life but not in adulthood.

conclusionsThese findings provide new insights into the pleiotropic architecture of impulsivity, its multifaceted biology, and its diverse relationships with mental health. The study underscores the importance of considering impulsivity as a genetically heterogeneous construct and highlights key neurodevelopmental pathways that shape its expression across the lifespan.

Indexed as

Genetic PleiotropyImpulsive BehaviorMental DisordersNeurodevelopmental DisordersAdultFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMultifactorial InheritanceBiological MarkersEpidemiologyGenetics/GenomicsImpulsivityNeurodevelopmental DisordersSubstance-Related and Addictive Disorders

Identifiers

PMID41152253
PMCPMC13587150

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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 OpenQuestion graph.