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Gene expression and DNA methylation are extensively coordinated with MRI-based brain microstructural characteristics.

Authors
  • Gaiteri, Chris1
  • Dawe, Robert2, 3
  • Mostafavi, Sara4
  • Blizinsky, Katherine D2, 5
  • Tasaki, Shinya2
  • Komashko, Vitalina2
  • Yu, Lei2
  • Wang, Yanling2
  • Schneider, Julie A2
  • Arfanakis, Konstantinos2, 3, 6
  • De Jager, Philip L7
  • Bennett, David A2
  • 1 Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. [email protected]
  • 2 Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
  • 3 Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, IL, USA.
  • 4 Department of Statistics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. , (Canada)
  • 5 National Institutes of Health, National Human Genome Research Institute, Bethesda, MD, USA.
  • 6 Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
  • 7 Columbia University College of Physicians and Surgeons, New York, NY, USA.
Type
Published Article
Journal
Brain Imaging and Behavior
Publisher
Springer-Verlag
Publication Date
Aug 01, 2019
Volume
13
Issue
4
Pages
963–972
Identifiers
DOI: 10.1007/s11682-018-9910-4
PMID: 29934819
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Cognitive function relies on both molecular levels and cellular structures. However, systematic relationships between these two components of cognitive function, and their joint contribution to disease, are largely unknown. We utilize postmortem neuroimaging in tandem with gene expression and DNA methylation, from 222 deeply-phenotyped persons in a longitudinal aging cohort. Expression of hundreds of genes and methylation at thousands of loci are related to the microstructure of extensive regions of this same set of brains, as assessed by MRI. The genes linked to brain microstructure perform functions related to cell motility, transcriptional regulation and nuclear processes, and are selectively associated with Alzheimer's phenotypes. Similar methodology can be applied to other diseases to identify their joint molecular and structural basis, or to infer molecular levels in the brain on the basis of neuroimaging for precision medicine applications.

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