Characterizing the Pleiotropic Architecture of Impulsivity and Its Links to Psychopathology and Neurodevelopment.
Objective: Impulsivity 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...
| Publicado en: | American Journal of Psychiatry Vol. 183; no. 1; pp. 31 - 48 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , |
| Formato: | Artículo |
| Publicado: |
American Psychiatric Publishing, Inc.
Jan2026
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| Materias: | |
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ssf&AN=190592611&site=ehost-live header: @attributes: shortDbName: ssf uiTerm: 190592611 longDbName: Social Sciences Full Text (H.W. Wilson) uiTag: AN controlInfo: bkinfo: jinfo: jid: 0002953X API jtl: American Journal of Psychiatry issn: 0002953X maglogo: N pubinfo: dt: Jan2026 vid: 183 iid: 1 pid: 37323 pub: American Psychiatric Publishing, Inc. artinfo: ui: 190592611 10.1176/appi.ajp.20240382 ppf: 31 ppct: 17 formats: tig: atl: Characterizing the Pleiotropic Architecture of Impulsivity and Its Links to Psychopathology and Neurodevelopment. aug: au: Mallard, Travis T. Tubbs, Justin D. Jennings, Mariela Zhang, Yingzhe Gustavson, Daniel E. Grotzinger, Andrew D. Westwater, Margaret L. Williams, Camille M. Fortgang, Rebecca G. Elson, Sarah L. Fontanillas, Pierre Davis, Lea K. Raznahan, Armin Tucker-Drob, Elliot M. Choi, Karmel W. Ge, Tian Smoller, Jordan W. Palmer, Abraham A. Sanchez-Roige, Sandra affil: Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN. Institute for Genomic Medicine, University of California San Diego, La Jolla. su: Impulsive personality Mental health Genetic engineering Pathological psychology Neural development Biocomplexity Gene expression profiling Genome-wide association studies sug: subj: Impulsive personality Mental health Genetic engineering Pathological psychology Offices of Mental Health Practitioners (except Physicians) Neural development Biocomplexity Gene expression profiling Genome-wide association studies keyword: Biological Markers Epidemiology Genetics/Genomics Impulsivity Neurodevelopmental Disorders Substance-Related and Addictive Disorders Biological Markers Epidemiology Genetics/Genomics Impulsivity Neurodevelopmental Disorders Substance-Related and Addictive Disorders ab: Objective: Impulsivity 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. Methods: The 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. Results: The 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. Conclusions: These 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. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: N holdings: @attributes: islocal: N |
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