Evidence map›Paper›PMID 40036321›Full record

ArticleSchizophrenia bulletin2026

Polygenic Resilience Scores are Associated With Lower Penetrance of Schizophrenia Risk Genes, Protection Against Psychiatric and Medical Disorders, and Enhanced Mental Well-Being and Cognition.

Jonathan L Hess, Eric J Barnett, Jiahui Hou, Stephen V Faraone, Stephen J Glatt

Abstract read
In one paragraph

Article in Schizophrenia bulletin, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Neuropsychiatry genetics in Africa.Nature communications · 2026
    Review
  2. Article
  3. Polygenic scores in psychiatric research and clinical practice.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
    Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Jonathan L HessDepartment of Psychiatry and Behavioral Sciences, Norton College of Medicine at SUNY Upstate Medical University, Syracuse, NY 13210, United States.
Eric J BarnettDepartment of Psychiatry and Behavioral Sciences, Norton College of Medicine at SUNY Upstate Medical University, Syracuse, NY 13210, United States.
Jiahui HouDepartment of Psychiatry and Behavioral Sciences, Norton College of Medicine at SUNY Upstate Medical University, Syracuse, NY 13210, United States.
Stephen V FaraoneDepartment of Psychiatry and Behavioral Sciences, Norton College of Medicine at SUNY Upstate Medical University, Syracuse, NY 13210, United States.
Stephen J GlattDepartment of Psychiatry and Behavioral Sciences, Norton College of Medicine at SUNY Upstate Medical University, Syracuse, NY 13210, United States.

Funding

SLE Treatment with N-acetylcysteineU01AR076092 · NIAMS · UPSTATE MEDICAL UNIVERSITY · PI Michael P McDermott, Andras Perl · 2020 to 2026
$7.9M
Person-centered diagnostics and prediction for child dysregulatory psychopathology using novel phenotypesU01MH135970 · NIMH · OREGON HEALTH & SCIENCE UNIVERSITY · PI KARALUNAS, SARAH LYN, NAGEL, BONNIE J. · 2024 to 2025
$6.5M
Discoveries in ADHD genomics: Help or hype in clinical settings?R01MH116037 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI DOYLE, ALYSA E · 2019 to 2023
$4.4M
Genetic Predictors, Transcriptomic Biomarkers, & Neurobiological Signatures of Resilience to Alzheimer's DiseaseR01AG064955 · NIA · UPSTATE MEDICAL UNIVERSITY · PI FENNEMA-NOTESTINE, CHRISTINE, GLATT, STEPHEN J · 2019 to 2023
$3.8M
Longitudinal Family/Molecular Genetic Study to Validate Research Domain CriteriaR01MH101519 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI FARAONE, STEPHEN V, GLATT, STEPHEN J · 2014 to 2018
$3.5M
Polygenic and environmental contributions to ADHD trajectory and outcome from childhood through adolescenceR01MH131685 · NIMH · OREGON HEALTH & SCIENCE UNIVERSITY · PI Michael A Mooney, Molly Nikolas · 2023 to 2026
$3.1M
Leveraging computational strategies to disentangle the genetic and neural underpinnings of ADHD and its associated cognitive systemsR01MH130899 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI Tian Ge · 2023 to 2026
$3.0M
Gene Expression Biomarkers for Early Identification of Mild Cognitive Impairment: A Twin StudyR01AG054002 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLATT, STEPHEN J, TSUANG, MING T. · 2016 to 2019
$2.7M
Integrating Genetic, Neuroimaging, Transcriptomic, and Clinical Risk Factors as Multivariate Predictors of Cognitive Deterioration in Alzheimer's Disease.R01NS128535 · NINDS · UPSTATE MEDICAL UNIVERSITY · PI HESS, JONATHAN · 2022 to 2024
$1.2M
Profiling the Functional Genetics of Health and Disease using BrainGENIE: The Brain Gene Expression and Network Imputation EngineR21MH126494 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI GLATT, STEPHEN J, HESS, JONATHAN · 2021 to 2022
$446k
European Union's Horizon 2020 research and innovation program 1R01MH130899European Union's Horizon 2020 research and innovation program 1R01NS128535European Union's Horizon 2020 research and innovation program R01MH131685European Union's Horizon 2020 research and innovation program R0MH116037European Union's Horizon 2020 research and innovation program U01AR076092European Union's Horizon 2020 research and innovation program U01MH135970NIAMS NIH HHS U01 AR076092NIA NIH HHS R01 AG054002NIA NIH HHS R01 AG064955NIMH NIH HHS R01 MH101519NIMH NIH HHS R01 MH116037NIMH NIH HHS R01 MH130899NIMH NIH HHS R01 MH131685NIMH NIH HHS R21 MH126494NIMH NIH HHS R21MH126494NIMH NIH HHS U01 MH135970NINDS NIH HHS R01 NS128535U.S. National Instit€ute of Neurological Disorders and Stroke R01NS128535U.S. National Institutes of Health R01AG054002U.S. National Institutes of Health R01AG064955U.S. National Institutes of Health R01MH101519U.S. National Institutes of Health R21MH126494
6 · The paper itself

Abstract

background and hypothesisIn the past decade, significant advances have been made in finding genomic risk loci for schizophrenia (SCZ). This, in turn, has enabled the search for SCZ resilience loci that mitigate the impact of SCZ risk genes. We identified the first genomic resilience profile for SCZ, completely independent from known risk loci for SCZ, though it remains unclear whether resilience loci foster protection against adverse states associated with SCZ involving clinical, cognitive, and brain-structural phenotypes. STUDY

designWe analyzed genomic and phenotypic data from 459 784 participants from the UK Biobank, using regression models to estimate interaction effects of resilience and SCZ risk scores on phenotypes spanning multiple scales. STUDY

resultsWe found that resilience loci for SCZ afforded protection against lifetime psychiatric (schizophrenia, bipolar disorder, anxiety, and depression) and medical disorders (such as type 2 diabetes, cardiovascular, and digestive and metabolic disorders). Resilience loci also moderated the impact of SCZ loci, associated with protection against self-harm behavior and greater fluid intelligence scores. The main effects of resilience are also observed in the absence of a moderating effect in some instances, such as associations with larger brain structures.

conclusionsOverall, this study highlights a wide range of phenotypes that are significantly associated with resilience loci within the general population, revealing distinct patterns separate from those associated with SCZ risk loci. Resilience loci may protect against serious psychiatric and medical outcomes, comorbidities, and cognitive impairment. Therefore, it is conceivable that resilience loci facilitate adaptive processes linked to improved health and life expectancy.

Indexed as

Bipolar DisorderMetabolic DiseasesMultifactorial InheritancePenetranceResilience, PsychologicalSchizophreniaSelf-Injurious BehaviorAdultCardiovascular DiseasesFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreHumansMaleMiddle AgedPsychological Well-Beingbiobankbipolar disorderdepressiongenome-wide association studyhigh riskpolygenic scoreresilienceschizophreniasuicide

Identifiers

PMID40036321
PMCPMC13645839

What OpenQuestion 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 OpenQuestion graph.