Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA–DTI working group

Jahanshad, Neda, Kochunov, Peter V., Sprooten, Emma, Mandl, René C., Nichols, Thomas E., Almassy, Laura, Blangero, John, Brouwer, Rachel M., Curran, Joanne E., de Zubicaray, Greig I., Duggirala, Ravi, Fox, Peter T., Hong, L. Elliot, Landman, Bennett A., Martin, Nicholas G., McMahon, Katie L., Medland, Sarah E., Mitchell, Braxton D., Olvera, Rene L., Peterson, Charles P., Starr, John M., Sussmann, Jessika E., Toga, Arthur W., Wardlaw, Joanna M., Wright, Margaret J., Hulshoff Pol, Hilleke E., Bastind, Mark E., McIntosh, Andrew M., Deary, Ian J., Thompson, Paul M. and Glahn, David C. (2013) Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA–DTI working group. NeuroImage, 81 455-469. doi:10.1016/j.neuroimage.2013.04.061


Author Jahanshad, Neda
Kochunov, Peter V.
Sprooten, Emma
Mandl, René C.
Nichols, Thomas E.
Almassy, Laura
Blangero, John
Brouwer, Rachel M.
Curran, Joanne E.
de Zubicaray, Greig I.
Duggirala, Ravi
Fox, Peter T.
Hong, L. Elliot
Landman, Bennett A.
Martin, Nicholas G.
McMahon, Katie L.
Medland, Sarah E.
Mitchell, Braxton D.
Olvera, Rene L.
Peterson, Charles P.
Starr, John M.
Sussmann, Jessika E.
Toga, Arthur W.
Wardlaw, Joanna M.
Wright, Margaret J.
Hulshoff Pol, Hilleke E.
Bastind, Mark E.
McIntosh, Andrew M.
Deary, Ian J.
Thompson, Paul M.
Glahn, David C.
Title Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA–DTI working group
Journal name NeuroImage   Check publisher's open access policy
ISSN 1053-8119
1095-9572
Publication date 2013-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.neuroimage.2013.04.061
Open Access Status Not yet assessed
Volume 81
Start page 455
End page 469
Total pages 15
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 2808 Neurology
2805 Cognitive Neuroscience
Abstract The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA-DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18-85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies.
Keyword Diffusion Tensor Imaging (DTI)
Heritability
Imaging genetics
Meta-analysis
Multi-site
Reliability
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID NHMRC 486682
EB008432
FT0991634
087727/Z/08/Z
R01 HD050735
R01 EB015611
MH0708143
MH083824
MH078111
MH59490
Institutional Status UQ

 
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Created: Tue, 18 Jun 2013, 20:01:35 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging