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Genetic variants associated with longitudinal changes in brain structure across the lifespan

  • the IMAGEN Consortium
  • Utrecht University
  • Vrije Universiteit Amsterdam
  • University of California at San Diego
  • Radboud University Nijmegen
  • Queensland Institute of Medical Research
  • University of Southern California
  • American Psychiatric Association
  • VA Medical Center
  • University of California at Los Angeles
  • Biogen IDEC
  • Leiden University
  • Complutense University
  • University of Oslo
  • Université Paris Saclay
  • Hospital Universitario Marques de Valdecilla
  • San Juan de Dios Sanitary Park
  • Universidad de Cantabria
  • King's College London
  • University of Edinburgh
  • Erasmus University Rotterdam
  • The University of Sydney
  • University of Greifswald
  • University of Galway
  • Pontificia Universidad Católica de Chile
  • University of Münster
  • Technische Universität Dresden
  • Université Paris-Saclay
  • University of Groningen
  • University of Cape Town
  • Departments of Experimental and Clinical Psychology
  • Heidelberg University 
  • Physikalisch-Technische Bundesanstalt
  • VU University Medical Center
  • Fudan University
  • University of New South Wales
  • Jülich Research Centre
  • Heinrich Heine University Düsseldorf
  • Ludwig Maximilian University of Munich
  • Munich Center for Neurosciences (MCN) – Brain & Mind
  • University of New Mexico
  • Neuroscience Research Australia
  • University of Göttingen
  • The University of Auckland
  • Brain Research New Zealand - Rangahau Roro Aotearoa
  • University of Basel
  • Friedrich Schiller University Jena
  • Valdecilla Biomedical Research Institute IDIVAL
  • Sorbonne Université
  • Martin Luther University Halle-Wittenberg
  • Imperial College London
  • University of Marburg
  • National Institutes of Health
  • Wakayama Medical University
  • Instituto de Física de Cantabria
  • German Center for Neurodegenerative Diseases
  • Universidade Federal de São Paulo
  • CNPq
  • Curtin University
  • University of Bonn
  • University of Bergen
  • University of North Carolina at Chapel Hill
  • Maastricht University
  • South London and Maudsley NHS Foundation Trust
  • University of Montreal
  • University of Toronto
  • Universidad Adolfo Ibáñez
  • Karolinska Institutet
  • Diakonhjemmet Hospital
  • University of Melbourne
  • National Ageing Research Institute
  • Trinity College Dublin
  • Instituto Ame Sua Mente
  • Karakter Child and Adolescent Psychiatry University Centre
  • Altrecht
  • University of Seville
  • A Platform for Scientific Excellence (SINAPSE) Collaboration
  • Oslo New University College
  • Max Planck Institute for Psycholinguistics
  • University of Vermont
  • University of Nottingham
  • Charité – Universitätsmedizin Berlin
  • University of Plymouth
  • Icahn School of Medicine at Mount Sinai
  • Institut des Maladies Neurodégénératives
  • University Hospital of Schleswig-Holstein
  • University of Amsterdam
  • Prince of Wales Hospital
  • Universidade Federal do Rio Grande do Sul
  • Singapore Institute of Mental Health
  • National University of Singapore
  • Berlin Institute of Health at Charité - Universitätsmedizin Berlin
  • University of Queensland

Research output: Contribution to journalArticlepeer-review

Abstract

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

Original languageEnglish
Pages (from-to)421-432
Number of pages12
JournalNature Neuroscience
Volume25
Issue number4
DOIs
Publication statusPublished - 5 Apr 2022
Externally publishedYes

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