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Extending Genetic Linkage Analysis to Diffusion Tensor Images to Map Single Gene Effects on Brain Fiber Architecture

  • Ming-Chang Chiang
  • Christina Avedissian
  • Marina Barysheva
  • Arthur W. Toga
  • Katie L. McMahon
  • Greig I. de Zubicaray
  • Margaret J. Wright
  • Paul M. Thompson
Part of the Lecture Notes in Computer Science book series (LNCS, volume 5762)

Abstract

We extended genetic linkage analysis - an analysis widely used in quantitative genetics - to 3D images to analyze single gene effects on brain fiber architecture. We collected 4 Tesla diffusion tensor images (DTI) and genotype data from 258 healthy adult twins and their non-twin siblings. After high-dimensional fluid registration, at each voxel we estimated the genetic linkage between the single nucleotide polymorphism (SNP), Val66Met (dbSNP number rs6265), of the BDNF gene (brain-derived neurotrophic factor) with fractional anisotropy (FA) derived from each subject’s DTI scan, by fitting structural equation models (SEM) from quantitative genetics. We also examined how image filtering affects the effect sizes for genetic linkage by examining how the overall significance of voxelwise effects varied with respect to full width at half maximum (FWHM) of the Gaussian smoothing applied to the FA images. Raw FA maps with no smoothing yielded the greatest sensitivity to detect gene effects, when corrected for multiple comparisons using the false discovery rate (FDR) procedure. The BDNF polymorphism significantly contributed to the variation in FA in the posterior cingulate gyrus, where it accounted for around 90-95% of the total variance in FA. Our study generated the first maps to visualize the effect of the BDNF gene on brain fiber integrity, suggesting that common genetic variants may strongly determine white matter integrity.

Keywords

Structural Equation Model Fractional Anisotropy Diffusion Tensor Image BDNF Gene Posterior Cingulate Gyrus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Ming-Chang Chiang
    • 1
  • Christina Avedissian
    • 1
  • Marina Barysheva
    • 1
  • Arthur W. Toga
    • 1
  • Katie L. McMahon
    • 2
  • Greig I. de Zubicaray
    • 2
  • Margaret J. Wright
    • 3
  • Paul M. Thompson
    • 1
  1. 1.Laboratory of Neuro Imaging, Dept. of NeurologyUCLA School of MedicineLos Angeles
  2. 2.Functional Magnetic Resonance Imaging Laboratory, Centre for Magnetic ResonanceUniversity of QueenslandBrisbaneAustralia
  3. 3.Queensland Institute of Medical ResearchBrisbaneAustralia

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