Common genetic variants influence human subcortical brain structures

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • for the Alzheimer's Disease Neuroimaging Initiative - (Autor:in)
  • The CHARGE Consortium - (Autor:in)
  • EPIGEN - (Autor:in)
  • IMAGEN Consortium - (Autor:in)
  • Saguenay Youth Study (SYS) Group - (Autor:in)
  • Stefan Ehrlich - , Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Massachusetts General Hospital (Autor:in)
  • Andreas Heinz - , Universität Bonn (Autor:in)
  • 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
  • Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
  • Ernst-Moritz-Arndt-Universität 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 University Hospital
  • Universität Heidelberg
  • Max Planck Institute for Psycholinguistics
  • Medizinische Fakultät Carl Gustav Carus Dresden
  • National Institutes of Health (NIH)
  • Yale University
  • Indiana University-Purdue University Indianapolis
  • Georg-August-Universität Göttingen
  • Broad Institute of Harvard University and MIT
  • Harvard University
  • Universität Aarhus
  • H. Lundbeck A/S
  • University College London
  • Hospital Universitario Marques de Valdecilla
  • CIBER - Centro de Investigación Biomédica en Red
  • 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

OriginalspracheEnglisch
Seiten (von - bis)224-229
Seitenumfang6
FachzeitschriftNature
Jahrgang520
Ausgabenummer7546
PublikationsstatusElektronische Veröffentlichung vor Drucklegung - 21 Jan. 2015
Peer-Review-StatusJa

Externe IDs

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

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete