Extending genetic linkage analysis to diffusion tensor images to map single gene effects on brain fiber architecture

Chiang, M. C., Avedissian, C., Barysheva, M., Toga, A. W., McMahon, K. L., de Zubicaray, G. I., Wright, M. J., & Thompson, P. M. (2009) Extending genetic linkage analysis to diffusion tensor images to map single gene effects on brain fiber architecture. In Yang, Guang-Zhong, Hawkes, David, Rueckert, Daniel, Noble, Alison, & Taylor, Chris (Eds.) Medical Image Computing and Computer-Assisted Intervention – MICCAI 2009: 12th International Conference, London, UK, September 20-24, 2009, Proceedings, Part II, Springer Berlin Heidelberg, London, UK, pp. 506-513.

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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.

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ID Code: 85695
Item Type: Conference Paper
Refereed: Yes
DOI: 10.1007/978-3-642-04271-3_62
ISBN: 9783642042713
ISSN: 0302-9743
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2009 Springer-Verlag
Deposited On: 23 Oct 2015 02:35
Last Modified: 29 Oct 2015 02:34

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