ArticleProceedings of the National Academy of Sciences of the United States of America2023
Genomic loci influence patterns of structural covariance in the human brain.
Open access · hybridAbstract read
In one paragraph
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 35 citations in OpenAlex.
- Chemical language models for early-stage drug discovery: applications, pitfalls, and future directions.Journal of computer-aided molecular design · 2026Review
- Sex-specific biological aging clocks across organs and omics.Nature medicine · 2026Article
- A dual-targeted mitochondria and lipid droplets near-infrared probe for visualizing viscosity and sulfur dioxide fluctuations during inflammatory microenvironment.Mikrochimica acta · 2026Article
- Crosstalk between Ryanodine Receptor 2 Dysfunction and FK506-Binding Proteins in Pulmonary Hypertension.Cardiovascular drugs and therapy · 2026Review
- Batch Effect Correction for Neuroimaging Data with Heterogeneous Spatial Correlations.bioRxiv : the preprint server for biology · 2026Article
- Brain-heart-eye axis revealed by multi-organ imaging genetics and proteomics.Nature biomedical engineering · 2026Article
- Article
- Coupled cross-sectional and longitudinal non-negative matrix factorization reveals dominant brain aging trajectories in 48,949 individuals.Nature communications · 2026Article
- Learning heritable multimodal brain representation via contrastive learning.Research square · 2026Article
- Computation and resource efficient genome-wide association analysis for large-scale imaging studies.Nature communications · 2026Article
- Learning heritable multimodal brain representation via contrastive learning.bioRxiv : the preprint server for biology · 2026Article
- Multi-organ AI endophenotypes chart the heterogeneity of brain, eye and heart pan-disease.Nature. Mental health · 2026Article
- MRI-based multi-organ clocks for healthy aging and disease assessment.Nature medicine · 2026Article
- Taming dimensionality in big neuroimaging data: Efficient orthonormal projective NMF via stochastic learning and data compression.Imaging neuroscience (Cambridge, Mass.) · 2026Article
- Revolutionizing Neurodegenerative Disease Management: The Synergy of AI and Pharmacy.Current aging science · 2026Review
- Computation and resource efficient genome-wide association analysis for large-scale imaging studies.medRxiv : the preprint server for health sciences · 2025Article
- Neuroimaging endophenotypes reveal underlying mechanisms and genetic factors contributing to progression and development of four brain disorders.Nature biomedical engineering · 2025Article
- Refining the generation, interpretation and application of multi-organ, multi-omics biological aging clocks.Nature aging · 2025Article
- Sleep chart of biological aging clocks across organs and omics.medRxiv : the preprint server for health sciences · 2025Article
- Multi-organ MRI digitizes biological aging clocks across proteomics, metabolomics, and genetics.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
66 authors at 20 institutions in 10 countries.
Junhao WenLaboratory of AI and Biomedical Science, Department of Neurology, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033.ORCID 0000-0003-2077-3070
Ilya M NasrallahAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0003-2346-7562
Ahmed AbdulkadirAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0003-4679-8081
Theodore D SatterthwaiteAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0001-7072-9399
Zhijian YangAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Guray ErusAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Timothy Robert-FitzgeraldPenn Statistics in Imaging and Visualization Center, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0001-8303-8001
Ashish SinghAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Aristeidis SotirasDepartment of Radiology, Washington University School of Medicine, St. Louis, MO 63110.ORCID 0000-0003-0795-8820
Aleix Boquet-PujadasBiomedical Imaging Group, Department of Biomedical Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
Elizabeth MamourianAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Jimit DoshiAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Yuhan CuiAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Dhivya SrinivasanAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Ioanna SkampardoniAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Jiong ChenAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Gyujoon HwangAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Mark BergmanAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Jingxuan BaoDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104.
Yogasudha VeturiDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-5878-2960
Zhen ZhouAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Shu YangDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104.
Paola DazzanDepartment of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, United Kingdom.
Rene S KahnDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Hugo G SchnackDepartment of Psychiatry, University Medical Center Utrecht, Utrecht 3584 CX Ut, Netherlands.
Marcus V ZanettiInstitute of Psychiatry, Department of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo 05508-070, Brazil.
Eva MeisenzahlDepartment of Psychiatry and Psychotherapy, Heinrich Heine University, Düsseldorf 40204, Germany.
Geraldo F BusattoInstitute of Psychiatry, Department of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo 05508-070, Brazil.ORCID 0000-0003-4749-4602
Benedicto Crespo-FacorroHospital Universitario Virgen del Rocio, School of Medicine, University of Sevilla, Sevilla 41004, Spain.
Christos PantelisMelbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC 3052, Australia.ORCID 0000-0002-9565-0238
Stephen J WoodOrygen and the Centre for Youth Mental Health, Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC 3052, Australia.
Chuanjun ZhuoKey Laboratory of Real Tine Tracing of Brain Circuits in Psychiatry and Neurology, Department of Psychiatry, Tianjin Medical University, Tianjin 300070, China.
Russell T ShinoharaAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0001-8627-8203
Ruben C GurDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-9657-1996
Raquel E GurDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-4082-8502
Nikolaos KoutsoulerisDepartment of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich 80539, Germany.
Daniel H WolfAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Andrew J SaykinIndiana Alzheimer's Disease Research Center, Department of Radiology, Indiana University School of Medicine, Indianapolis, IN 46202-3082.ORCID 0000-0002-1376-8532
Marylyn D RitchieDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Li ShenDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104.ORCID 0000-0002-5443-0503
Paul M ThompsonImaging Genetics Center, Department of Neurology, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033.
Olivier ColliotInstitut du Cerveau, Sorbonne Université, Paris 75013, France.
Katharina WittfeldDepartment of Psychiatry and Psychotherapy, German Center for Neurodegenerative Diseases, University Medicine Greifswald, Greifswald 17475, Germany.ORCID 0000-0003-4383-5043
Hans J GrabeDepartment of Psychiatry and Psychotherapy, German Center for Neurodegenerative Diseases, University Medicine Greifswald, Greifswald 17475, Germany.
Duygu TosunDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94143.
Murat BilgelLaboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Baltimore 21224, MD.ORCID 0000-0001-5042-7422
Yang AnLaboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Baltimore 21224, MD.
Daniel S MarcusDepartment of Radiology, Washington University School of Medicine, St. Louis, MO 63110.
Pamela LaMontagneDepartment of Radiology, Washington University School of Medicine, St. Louis, MO 63110.
Susan R HeckbertDepartment of Epidemiology, University of Washington, Seattle, WA 98195.ORCID 0000-0002-7100-512X
Thomas R AustinDepartment of Epidemiology, University of Washington, Seattle, WA 98195.
Lenore J LaunerNeuroepidemiology Section, Intramural Research Program, National Institute on Aging, Washington, MD 20817.ORCID 0000-0002-3238-7612
Mark EspelandSticht Center for Healthy Aging and Alzheimer's Prevention, Divisions of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101.ORCID 0000-0002-3711-1949
Colin L MastersFlorey Institute of Neuroscience and Mental Health, Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia.ORCID 0000-0003-3072-7940
Paul MaruffFlorey Institute of Neuroscience and Mental Health, Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia.ORCID 0000-0002-6947-9537
Jurgen FrippHealth and Biosecurity, Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation, Brisbane, QLD 4029, Australia.
Sterling C JohnsonWisconsin Alzheimer's Institute, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792.
John C MorrisKnight Alzheimer Disease Research Center, Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110.
Marilyn S AlbertDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
R Nick BryanDepartment of Radiology, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0002-2327-4579
Susan M ResnickLaboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Baltimore 21224, MD.
Yong FanAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.ORCID 0000-0001-9869-4685
Mohamad HabesGlenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229.ORCID 0000-0001-9447-5805
David WolkAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Haochang ShouAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
Christos DavatzikosAI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
University of Pennsylvania · USNational Institute on Aging · USThe University of Melbourne · AUWashington University in St. Louis · USGerman Center for Neurodegenerative Diseases · DEUniversidade de São Paulo · BRUniversity of Southern California · USUniversity of Washington · USCommonwealth Scientific and Industrial Research Organisation · AUÉcole Polytechnique Fédérale de Lausanne · CHHeinrich Heine University Düsseldorf · DEHospital Universitario Virgen del Rocío · ESIcahn School of Medicine at Mount Sinai · USIndiana University School of MedicineJohns Hopkins University · USKing's College London · GBLudwig-Maximilians-Universität München · DESorbonne Université · FRThe University of Texas Health Science Center at San Antonio · USTianjin Medical University · CN
Funding
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MResearch Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3MResearch Education ComponentP30AG072976 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI ANDREW J SAYKIN · 2021 to 2026
$24.1MUltrascale Machine Learning to Empower Discovery in Alzheimers Disease BiobanksU01AG068057 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Christos Davatzikos, Heng Huang · 2020 to 2026
$20.7MKBASE2: Korean Brain Aging Study, Longitudinal Endophenotypes and Systems BiologyU01AG072177 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI LEE, DONG YOUNG, NHO, KWANGSIK TIMOTHY · 2021 to 2025
$11.2MMemory Circuitry in MCI and Early Alzheimer’s Disease Prodrome: Molecular DriversR01AG019771 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 2001 to 2021
$6.9MMachine Learning and Large-scale Imaging analytics for dimensional representations of brain trajectories in aging and preclinical Alzheimer's Disease: The brain aging chart and the iSTAGING consortiumRF1AG054409 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVATZIKOS, CHRISTOS · 2017 to 2023
$6.3MLeveraging Neuroimaging Biomarkers to Understand the Role of Social Networks in Alzheimer's DiseaseR01AG057739 · NIA · TRUSTEES OF INDIANA UNIVERSITY · PI APOSTOLOVA, LIANA G, PERRY, BREA LOUISE · 2018 to 2022
$3.5MMultiethnic machine learning brain signatures of ADRDR01AG080821 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HABES, MOHAMAD · 2022 to 2025
$2.9MCognitive Aging, Alzheimers disease, and Cancer-related Cognitive DeclineR01AG068193 · NIA · GEORGETOWN UNIVERSITY · PI MANDELBLATT, JEANNE, SAYKIN, ANDREW J · 2020 to 2023
$2.8MTraining Grant on Alzheimer's Disease and ADRD at Indiana UniversityT32AG071444 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI GARY E. LANDRETH, Bruce T Lamb · 2021 to 2026
$2.8MMapping Heterogeneity of Neuroanatomical Imaging Signatures of Psychosis via Pattern AnalysisR01MH112070 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI DAVATZIKOS, CHRISTOS · 2017 to 2020
$2.7MNIA NIH HHS P30 AG010133NIA NIH HHS P30 AG072976NIA NIH HHS R01 AG019771NIA NIH HHS R01 AG057739NIA NIH HHS R01 AG068193NIA NIH HHS R01 AG080821NIA NIH HHS RF1 AG054409NIA NIH HHS T32 AG071444NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG068057NIA NIH HHS U01 AG072177NIDA NIH HHS HHSN271201600059CNIH HHS S10 OD023495NIMH NIH HHS R01 MH112070NLM NIH HHS R01 LM013463
Abstract
Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and appendage development, while pathways of breast cancer indicate potential interplays between brain metastasis and PSCs associated with neurodegeneration and dementia. Using support vector machines, multi-scale PSCs effectively derive imaging signatures of several brain diseases. Our results elucidate genetic and biological underpinnings that influence structural covariance patterns in the human brain.
Indexed as
Brain NeoplasmsMagnetic Resonance ImagingBrainBrain MappingGenomicsHumansimaging geneticsmatrix factorizationstructural covariance
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-ND
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.