Common genetic variants influence human subcortical brain structures

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Keck School of Medicine at University of Southern California
  • University of California at Los Angeles
  • Queensland Institute of Medical Research
  • Radboud University Nijmegen
  • King's College London (KCL)
  • Institut Pasteur Paris
  • Université Paris Cité
  • German Center for Neurodegenerative Diseases (DZNE)
  • University of Greifswald
  • Utrecht University
  • Umeå University
  • University of Edinburgh
  • Lagos State University
  • University of New South Wales
  • University of Sydney
  • University of Toronto
  • University of Oslo
  • McGill University
  • Lieber Institute for Brain Development
  • Vrije Universiteit Amsterdam (VU)
  • University of Bergen
  • Haukeland universitets­sjukehus
  • Heidelberg University 
  • Max Planck Institute for Psycholinguistics
  • Medical Faculty Carl Gustav Carus
  • National Institutes of Health (NIH)
  • Yale University
  • Indiana University-Purdue University Indianapolis
  • University of Göttingen
  • Broad Institute of Harvard University and MIT
  • Harvard University
  • Aarhus University
  • H. Lundbeck A/S
  • University College London
  • Hospital Universitario Marques de Valdecilla
  • CIBER - Center for Biomedical Research Network
  • Trinity College Dublin
  • Center for Translational Research on Adversity

Abstract

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08×10 -33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Details

Original languageEnglish
Pages (from-to)224-229
Number of pages6
JournalNature
Volume520
Issue number7546
Publication statusE-pub ahead of print - 21 Jan 2015
Peer-reviewedYes

External IDs

PubMed 25607358
ORCID /0000-0003-2132-4445/work/160950837

Keywords

Sustainable Development Goals

ASJC Scopus subject areas