Evidence map›Paper›PMID 37146461›Full record

ArticlePsychiatry research2023

Polygenic overlap with body-mass index improves prediction of treatment-resistant schizophrenia.

Kevin S O'Connell, Elise Koch, Hasan Çağın Lenk, Ibrahim A Akkouh, Guy Hindley, Piotr Jaholkowski, Robert Løvsletten Smith, Børge Holen, Alexey A Shadrin, Oleksandr Frei and 6 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychiatry research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 4% of its field
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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Genetic overlap between treatment-resistant schizophrenia and smoking initiation.The international journal of neuropsychopharmacology · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Polygenic overlap with granulocyte counts identifies novel loci for clozapine metabolism and clozapine-induced agranulocytosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
  10. Article
  11. Review
  12. Article
  13. 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

16 authors at 3 institutions in 3 countries.

Kevin S O'ConnellNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: kevin.oconnell@medisin.uio.no.
Elise KochNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Hasan Çağın LenkCenter for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway; Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.
Ibrahim A AkkouhNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Guy HindleyNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Psychosis Studies, Institute of Psychiatry, Psychology and Neurosciences, King's College London, United Kingdom.
Piotr JaholkowskiNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Robert Løvsletten SmithNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
Børge HolenNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Alexey A ShadrinNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental disorders, University of Oslo and Oslo University Hospital, Oslo, Norway.
Oleksandr FreiNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Center for Bioinformatics, Department of Informatics, University of Oslo, 0316 Oslo, Norway.
Olav B SmelandNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Nils Eiel SteenNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Anders M DaleDepartment of Radiology, University of California, San Diego, La Jolla, CA 92093, USA; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA 92093, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA.
Espen MoldenCenter for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway; Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.
Srdjan DjurovicDepartment of Medical Genetics, Oslo University Hospital, Oslo, Norway; NORMENT Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.
Ole A AndreassenNORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; KG Jebsen Centre for Neurodevelopmental disorders, University of Oslo and Oslo University Hospital, Oslo, Norway. Electronic address: ole.andreassen@medisin.uio.no.
Oslo University Hospital · NOUniversity of Oslo · NOUniversity of California San Diego · US

Funding

Spatiotemporal Brain Imaging: Microscopic &System LevelR01EB000790 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DALE, ANDERS M · 2002 to 2015
$15.3M
Neuronal, glial and BOLD fMRI signals: From BOLD to 2-photon microscopyR01NS057198 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DEVOR, ANNA · 2009 to 2017
$2.6M
3/7 Psychiatric Genomics Consortium: Advancing Discovery and ImpactR01MH124839 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ANDREASSEN, OLE A, HUCKINS, LAURA MARIANNE · 2021 to 2025
$2.0M
6/7 Psychiatric Genomics Consortium: Advancing Discovery and ImpactR01MH124875 · NIMH · TRINITY COLLEGE DUBLIN · PI Aiden Peter Corvin · 2021 to 2026
$765k
NIBIB NIH HHS R01 EB000790NIMH NIH HHS R01 MH124839NIMH NIH HHS R01 MH124875NINDS NIH HHS R01 NS057198
6 · The paper itself

Abstract

Treatment resistant schizophrenia (TRS) is characterized by repeated treatment failure with antipsychotics. A recent genome-wide association study (GWAS) of TRS showed a polygenic architecture, but no significant loci were identified. Clozapine is shown to be the superior drug in terms of clinical effect in TRS; at the same time it has a serious side effect profile, including weight gain. Here, we sought to increase power for genetic discovery and improve polygenic prediction of TRS, by leveraging genetic overlap with Body Mass Index (BMI). We analysed GWAS summary statistics for TRS and BMI applying the conditional false discovery rate (cFDR) framework. We observed cross-trait polygenic enrichment for TRS conditioned on associations with BMI. Leveraging this cross-trait enrichment, we identified 2 novel loci for TRS at cFDR <0.01, suggesting a role of MAP2K1 and ZDBF2. Further, polygenic prediction based on the cFDR analysis explained more variance in TRS when compared to the standard TRS GWAS. These findings highlight putative molecular pathways which may distinguish TRS patients from treatment responsive patients. Moreover, these findings confirm that shared genetic mechanisms influence both TRS and BMI and provide new insights into the biological underpinnings of metabolic dysfunction and antipsychotic treatment.

Indexed as

Antipsychotic AgentsClozapineSchizophreniaBody Mass IndexGenome-Wide Association StudyHumansSchizophrenia, Treatment-ResistantAntipsychotic AgentsClozapineClozapineGWASPsychiatric geneticsTreatment response

Identifiers

PMID37146461
PMCPMC10788293
OpenAlexW4366748340

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.