Notes:
Multi-site genetic analysis of diffusion images and voxelwise
heritability analysis: a pilot project of the ENIGMA-DTI working
group.
Neuroimage. 2013 Nov 1;81:455-69.
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.
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