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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Utrecht University
  • Vrije Universiteit Amsterdam (VU)
  • 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
  • Leiden University
  • Complutense University
  • University of Oslo
  • Université Paris-Saclay
  • Hospital Universitario Marques de Valdecilla
  • CIBER - Center for Biomedical Research Network
  • Universidad de Cantabria
  • King's College London (KCL)
  • University of Edinburgh
  • Erasmus University Rotterdam
  • University of Sydney
  • University of Greifswald
  • University of Galway
  • Pontificia Universidad Católica de Chile
  • University of Münster
  • University of Groningen
  • University of Cape Town
  • Heidelberg University 

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.

Details

Original languageEnglish
Pages (from-to)421-432
Number of pages12
JournalNature neuroscience
Volume25
Issue number4
Publication statusPublished - Apr 2022
Peer-reviewedYes

External IDs

PubMed 35383335
ORCID /0000-0001-5398-5569/work/150329535
ORCID /0000-0002-8493-6396/work/150330256

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Library keywords