Evidence map›Paper›PMID 37582581›Full record

ArticleSchizophrenia bulletin2023

Psychosis Endophenotypes: A Gene-Set-Specific Polygenic Risk Score Analysis.

Baihan Wang, Haritz Irizar, Johan H Thygesen, Eirini Zartaloudi, Isabelle Austin-Zimmerman, Anjali Bhat, Jasmine Harju-Seppänen, Oliver Pain, Nick Bass, Vasiliki Gkofa and 38 more

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

Article in Schizophrenia bulletin, 2023. 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
1.3field-weighted citation impact, top 17% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  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

48 authors at 17 institutions in 10 countries.

Baihan WangDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.ORCID 0000-0001-6986-8236
Haritz IrizarDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.
Johan H ThygesenDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.
Eirini ZartaloudiDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.
Isabelle Austin-ZimmermanDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.
Anjali BhatDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.
Jasmine Harju-SeppänenDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.ORCID 0000-0002-9027-2119
Oliver PainDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0001-5680-3281
Nick BassDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.
Vasiliki GkofaDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.
Behrooz Z AlizadehUniversity of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center, Groningen, The Netherlands.
Therese van AmelsvoortDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Maria J ArranzFundació Docència i Recerca Mutua Terrassa, Terrassa, Spain.
Stephan BenderDepartment of Child and Adolescent Psychiatry, Psychosomatic Medicine and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Wiepke CahnDepartment of Psychiatry, Brain Centre Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.ORCID 0000-0002-0482-8759
Maria Stella CalafatoDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.ORCID 0000-0001-8757-635X
Benedicto Crespo-FacorroCIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Sevilla, Spain.
Marta Di FortiSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Genetic Risk and Outcome of Psychosis (GROUP) Study
Ina GieglingComprehensive Centers for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Austria.
Lieuwe de HaanDepartment of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Jeremy HallNeuroscience and Mental Health Innovation Institute, School of Medicine, Cardiff University, Hadyn Ellis Building, Mandy Road, Cardiff, UK.
Mei-Hua HallPsychosis Neurobiology Laboratory, Harvard Medical School, McLean Hospital, Belmont, MA, USA.
Neeltje van HarenDepartment of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Sophia's Children Hospital, Rotterdam, The Netherlands.
Conrad IyegbeDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
René S KahnDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Eugenia KravaritiInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Stephen M LawrieDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Kuang LinNuffield Department of Population Health, University of Oxford, Oxford, UK.
Jurjen J LuykxDepartment of Psychiatry, Brain Centre Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Ignacio MataFundacion Argibide, Pamplona, Spain.
Colm McDonaldThe Centre for Neuroimaging & Cognitive Genomics (NICOG) and NCBES Galway Neuroscience Centre, University of Galway, Galway, Ireland.
Andrew M McIntoshDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Robin M MurrayInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Psychosis Endophenotypes International Consortium (PEIC)
Marco PicchioniInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
John PowellInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Diana P PrataInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0002-4051-022X
Dan RujescuDepartment of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Bart P F RuttenDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Madiha ShaikhNorth East London Foundation Trust, London, UK.
Claudia J P SimonsDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.ORCID 0000-0002-7637-3589
Timothea ToulopoulouInstitute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Matthias WeisbrodDepartment of General Psychiatry, Center of Psychosocial Medicine, University of Heidelberg, Germany.
Ruud van WinkelDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Karoline KuchenbaeckerDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.ORCID 0000-0001-9726-603X
Andrew McQuillinDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.ORCID 0000-0003-1567-2240
Elvira BramonDepartment of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.ORCID 0000-0003-1369-5983
Mental Health Research UK · GBKing's College London · GBCentro de Investigación Biomédica en Red de Salud Mental · ESMaastricht University · NLUtrecht University · NLComprehensive Cancer Center Vienna · ATHarvard University · USMount Sinai Health System · USNorth East London NHS Foundation Trust · GBRoyal Edinburgh Hospital · GBUniversity of Lisbon · PTArkin · NLErasmus MC · NLHeidelberg University · DEIcahn School of Medicine at Mount Sinai · USUniversity Medical Center Groningen · NLUniversity of Cologne · DE

Funding

China Scholarship Council-University College London Joint Research Scholarship 747429Geestkracht program of the Dutch Health Research Council 10-000-1001Medical Research Council G1100583Medical Research Council New Investigator Award G0901310National Institute of Allergy and Infectious DiseasesNational Institute of Health Research UK NIHR200756National Institutes of Health. Isabelle Austin-Zimmerman G1100583
6 · The paper itself

Abstract

background and hypothesisEndophenotypes can help to bridge the gap between psychosis and its genetic predispositions, but their underlying mechanisms remain largely unknown. This study aims to identify biological mechanisms that are relevant to the endophenotypes for psychosis, by partitioning polygenic risk scores into specific gene sets and testing their associations with endophenotypes. STUDY

designWe computed polygenic risk scores for schizophrenia and bipolar disorder restricted to brain-related gene sets retrieved from public databases and previous publications. Three hundred and seventy-eight gene-set-specific polygenic risk scores were generated for 4506 participants. Seven endophenotypes were also measured in the sample. Linear mixed-effects models were fitted to test associations between each endophenotype and each gene-set-specific polygenic risk score. STUDY

resultsAfter correction for multiple testing, we found that a reduced P300 amplitude was associated with a higher schizophrenia polygenic risk score of the forebrain regionalization gene set (mean difference per SD increase in the polygenic risk score: -1.15 µV; 95% CI: -1.70 to -0.59 µV; P = 6 × 10-5). The schizophrenia polygenic risk score of forebrain regionalization also explained more variance of the P300 amplitude (R2 = 0.032) than other polygenic risk scores, including the genome-wide polygenic risk scores.

conclusionsOur finding on reduced P300 amplitudes suggests that certain genetic variants alter early brain development thereby increasing schizophrenia risk years later. Gene-set-specific polygenic risk scores are a useful tool to elucidate biological mechanisms of psychosis and endophenotypes, offering leads for experimental validation in cellular and animal models.

Indexed as

Bipolar DisorderPsychotic DisordersSchizophreniaEndophenotypesGenetic Predisposition to DiseaseHumansMultifactorial InheritanceRisk Factorsbipolar disorderEEGneurodevelopmentP300schizophrenia

Identifiers

PMID37582581
PMCPMC10686343
OpenAlexW4385828166

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.