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Genomic loci influence patterns of structural covariance in the human brain.
Wen, Junhao; Nasrallah, Ilya M; Abdulkadir, Ahmed; Satterthwaite, Theodore D; Yang, Zhijian; Erus, Guray; Robert-Fitzgerald, Timothy; Singh, Ashish; Sotiras, Aristeidis; Boquet-Pujadas, Aleix; Mamourian, Elizabeth; Doshi, Jimit; Cui, Yuhan; Srinivasan, Dhivya; Skampardoni, Ioanna; Chen, Jiong; Hwang, Gyujoon; Bergman, Mark; Bao, Jingxuan; Veturi, Yogasudha; Zhou, Zhen; Yang, Shu; Dazzan, Paola; Kahn, Rene S; Schnack, Hugo G; Zanetti, Marcus V; Meisenzahl, Eva; Busatto, Geraldo F; Crespo-Facorro, Benedicto; Pantelis, Christos; Wood, Stephen J; Zhuo, Chuanjun; Shinohara, Russell T; Gur, Ruben C; Gur, Raquel E; Koutsouleris, Nikolaos; Wolf, Daniel H; Saykin, Andrew J; Ritchie, Marylyn D; Shen, Li; Thompson, Paul M; Colliot, Olivier; Wittfeld, Katharina; Grabe, Hans J; Tosun, Duygu; Bilgel, Murat; An, Yang; Marcus, Daniel S; LaMontagne, Pamela; Heckbert, Susan R.
Affiliation
  • Wen J; Laboratory 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.
  • Nasrallah IM; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Abdulkadir A; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Satterthwaite TD; Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104.
  • Yang Z; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Erus G; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Robert-Fitzgerald T; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Singh A; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Sotiras A; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Boquet-Pujadas A; Penn Statistics in Imaging and Visualization Center, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Mamourian E; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Doshi J; Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110.
  • Cui Y; Biomedical Imaging Group, Department of Biomedical Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
  • Srinivasan D; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Skampardoni I; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Chen J; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Hwang G; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Bergman M; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Bao J; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Veturi Y; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Zhou Z; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Yang S; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104.
  • Dazzan P; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Kahn RS; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Schnack HG; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104.
  • Zanetti MV; Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, United Kingdom.
  • Meisenzahl E; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
  • Busatto GF; Department of Psychiatry, University Medical Center Utrecht, Utrecht 3584 CX Ut, Netherlands.
  • Crespo-Facorro B; Institute of Psychiatry, Department of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo 05508-070, Brazil.
  • Pantelis C; Department of Psychiatry and Psychotherapy, Heinrich Heine University, Düsseldorf 40204, Germany.
  • Wood SJ; Institute of Psychiatry, Department of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo 05508-070, Brazil.
  • Zhuo C; Hospital Universitario Virgen del Rocio, School of Medicine, University of Sevilla, Sevilla 41004, Spain.
  • Shinohara RT; Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC 3052, Australia.
  • Gur RC; Orygen and the Centre for Youth Mental Health, Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC 3052, Australia.
  • Gur RE; Key Laboratory of Real Tine Tracing of Brain Circuits in Psychiatry and Neurology, Department of Psychiatry, Tianjin Medical University, Tianjin 300070, China.
  • Koutsouleris N; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Wolf DH; Penn Statistics in Imaging and Visualization Center, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Saykin AJ; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Ritchie MD; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Shen L; Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich 80539, Germany.
  • Thompson PM; AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Colliot O; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Wittfeld K; Indiana Alzheimer's Disease Research Center, Department of Radiology, Indiana University School of Medicine, Indianapolis, IN 46202-3082.
  • Grabe HJ; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • Tosun D; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104.
  • Bilgel M; Imaging 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.
  • An Y; Institut du Cerveau, Sorbonne Université, Paris 75013, France.
  • Marcus DS; Department of Psychiatry and Psychotherapy, German Center for Neurodegenerative Diseases, University Medicine Greifswald, Greifswald 17475, Germany.
  • LaMontagne P; Department of Psychiatry and Psychotherapy, German Center for Neurodegenerative Diseases, University Medicine Greifswald, Greifswald 17475, Germany.
  • Heckbert SR; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94143.
Proc Natl Acad Sci U S A ; 120(52): e2300842120, 2023 Dec 26.
Article in En | MEDLINE | ID: mdl-38127979
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Magnetic Resonance Imaging Limits: Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2023 Type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Magnetic Resonance Imaging Limits: Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2023 Type: Article