SynthesisMolecular psychiatry2026
Association between polygenic risk for Major Depression and brain structure in a mega-analysis of 50,975 participants across 11 studies.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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.
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.
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Who cites it
1 citing paper in PubMed.
- Recent developments in imaging transcriptomics for psychiatric disorders.Psychoradiology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
55 authors.
Xueyi ShenDivision of Psychiatry, University of Edinburgh, Edinburgh, UK. Xueyi.shen@ed.ac.uk.ORCID http://orcid.org/0000-0002-0538-4774
Yara J ToendersErasmus School of Social and Behavioral Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-4117-1143
Laura K M HanCentre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0001-9647-3723
Antoine WeihsDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0002-7113-0027
Nina AlexanderDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
Till F M AndlauerDepartment of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-2917-5889
Katharina BroschDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.ORCID http://orcid.org/0000-0002-0526-8095
Andreas J ForstnerInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-1876-6368
Dominik GrotegerdInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Tim HahnInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0001-6541-3795
Marco HermesdorfInstitute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Norbert HostenInstitute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
Hamidreza JamalabadiDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.ORCID http://orcid.org/0000-0003-2485-2374
Susanne MeinertInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0003-2177-7161
Yuri MilaneschiDepartment of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-3697-6617
Philipp G SämannMax Planck Institute of Psychiatry, Munich, Germany.ORCID http://orcid.org/0000-0001-8523-3628
Frederike SteinDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
Aleks StolicynDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-1147-7539
Lea TeutenbergDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
Gladi ThngDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.
Mark J AdamsDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-3599-6018
Florian Thomas-OdenthalDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.ORCID http://orcid.org/0000-0003-4912-8307
Paula UsemannDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
Uwe VölkerInterfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Katharina WittfeldDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID http://orcid.org/0000-0003-4383-5043
Marisol Herrera-RiveroInstitute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0001-7064-9487
Yunxuan Jiang23andMe, San Francisco, CA, USA.
Chao Tian23andMe, San Francisco, CA, USA.
23andMe Research Team
Nynke A GroenewoldDepartment of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.ORCID http://orcid.org/0000-0002-0865-8427
Sheri-Michelle KoopowitzDepartment of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Lachlan T StrikePsychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Udo DannlowskiInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0002-0623-3759
Andreas JansenDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
Tilo KircherDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.ORCID http://orcid.org/0000-0002-2514-2625
Igor NenadićDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.ORCID http://orcid.org/0000-0002-0749-7473
Kang SimWest Region, Institute of Mental Health, Singapore, Singapore.
Benjamin StraubeDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.ORCID http://orcid.org/0000-0002-9837-0944
Henry VölzkeInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Dan J SteinDepartment of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.ORCID http://orcid.org/0000-0001-7218-7810
Sarah E MedlandPsychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0003-1382-380X
Klaus BergerInstitute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Hans J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Axel KrugDepartment of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-0564-2497
Katie L McMahonSchool of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0002-6357-615X
Greig de ZubicaraySchool of Psychology and Counselling, Queensland University of Technology, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0003-4506-0579
Elena PozziCentre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.
Dick J VeltmanDepartment of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Sophia I ThomopoulosImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Neda JahanshadImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Lianne SchmaalCentre for Youth Mental Health, The University of Melbourne, Parkville, VIC, Australia.ORCID http://orcid.org/0000-0001-9822-048X
Andrew M McIntoshDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-0198-4588
Heather C WhalleyDivision of Psychiatry, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-4505-8869
ENIGMA MDD working group
Funding
Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1MENIGMA Bipolar Initiative: A Global Study of Imaging Genomics & Clinical OutcomesR01MH129742 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Christopher Ching, PAUL M THOMPSON · 2022 to 2026
$3.0MGlobal studies into the Genetic Architecture of the Brain's White Matter Network through Harmonized and Coordinated Analyses in the ENIGMA-ConsortiumR01MH134004 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Neda Jahanshad · 2023 to 2026
$2.6MGenetic influences on the brain: A twin imaging studyR01HD050735 · NICHD · QUEENSLAND INSTITUTE OF MEDICAL RESEARCH · PI WRIGHT, MARGARET JANE · 2007 to 2011
$2.6MNeurobiologically-Based Subtyping of Multi-Cohort Samples with MDD and PTSD SymptomsR01MH129832 · NIMH · DUKE UNIVERSITY · PI MOREY, RAJENDRA A, SCHMAAL, LIANNE · 2022 to 2025
$2.3MChief Scientist Office (CSO) CZD/16/6Department of Health | National Health and Medical Research Council (NHMRC) 2017962DH | National Institute for Health Research (NIHR) RO1 MH129742DH | National Institute for Health Research (NIHR) RO1 MH129832NIBIB NIH HHS U54 EB020403NICHD NIH HHS R01 HD050735NIMH NIH HHS R01 MH129742NIMH NIH HHS R01 MH129832NIMH NIH HHS R01 MH134004Wellcome TrustWellcome Trust (Wellcome) 104036/Z/14/ZWellcome Trust (Wellcome) 216767/Z/19/ZWellcome Trust (Wellcome) 220857/Z/20/Z
Abstract
Major Depression (MD) is a prevalent, disabling and life-limiting condition. The neurobiological associations of genetic risk for MD remain under-explored in large samples, with no comprehensive mega-analysis conducted to date. Our study analysed data from 11 separate studies, encompassing 50,975 participants from the ENIGMA Major Depressive Disorder Working Group. We developed highly consistent genetic and neuroimaging protocols and applied these throughout all participating studies, together with rigorous genetic methods to remove overlap between the polygenic risk scores (PRS) training and testing samples. Elevated PRS for MD correlated with lower intracranial volume and lower global measure of cortical surface area (β
Indexed as
BrainMajor Depressive DisorderAdultFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMagnetic Resonance ImagingMaleMiddle AgedMultifactorial InheritanceNeuroimagingPolymorphism, Single NucleotideRisk Factors
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