Contributors: University of Southern California (USC); University of Pennsylvania; Washington University School of Medicine Saint Louis, MO; Ecole Polytechnique Fédérale de Lausanne (EPFL); King's College Hospital (KCH); Icahn School of Medicine at Mount Sinai New York (MSSM); University Medical Center Utrecht; Universidade de São Paulo = University of São Paulo (USP); Heinrich Heine Universität Düsseldorf = Heinrich Heine University Düsseldorf; Universidad de Sevilla = University of Seville; University of Melbourne; Tianjin Medical University; Ludwig Maximilian University Munich = Ludwig Maximilians Universität München (LMU); Indiana State University; Algorithms, models and methods for images and signals of the human brain = Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain ICM Paris (ARAMIS); Inria de Paris; Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); Universität Greifswald - University of Greifswald; University of California San Francisco (UC San Francisco); University of California (UC); National Institute on Aging Bethesda, USA (NIA); National Institutes of Health Bethesda, MD, USA (NIH); University of Washington Seattle; Wake Forest School of Medicine Winston-Salem; Wake Forest Baptist Medical Center; The Australian e-Health Research centre; Royal Brisbane and Women's Hospital; University of Wisconsin-Madison; Washington University in Saint Louis (WUSTL); Johns Hopkins University School of Medicine Baltimore; University of Texas Health Science Center; The University of Texas Health Science Center at Houston (UTHealth); ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019)
نبذة مختصرة : International audience ; 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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