Identifying candidate gene effects by restricting search space in a multivariate genetic analysis of white matter microstructure

Warstadt, N. M., Jahanshad, N., Dennis, E. L., Kohannim, O., McMahon, K. L., de Zubicaray, G. I., Montgomery, G. W., Henders, A. K., Martin, N. G., Whitfield, J. B., Wright, M. J., & Thompson, P. M. (2014) Identifying candidate gene effects by restricting search space in a multivariate genetic analysis of white matter microstructure. In 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI 2014) : Beijing, China, 29 April - 2 May 2014., IEEE, Beijing, China.

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Several genetic variants are thought to influence white matter (WM) integrity, measured with diffusion tensor imaging (DTI). Voxel based methods can test genetic associations, but heavy multiple comparisons corrections are required to adjust for searching the whole brain and for all genetic variants analyzed. Thus, genetic associations are hard to detect even in large studies. Using a recently developed multi-SNP analysis, we examined the joint predictive power of a group of 18 cholesterol-related single nucleotide polymorphisms (SNPs) on WM integrity, measured by fractional anisotropy. To boost power, we limited the analysis to brain voxels that showed significant associations with total serum cholesterol levels. From this space, we identified two genes with effects that replicated in individual voxel-wise analyses of the whole brain. Multivariate analyses of genetic variants on a reduced anatomical search space may help to identify SNPs with strongest effects on the brain from a broad panel of genes.

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ID Code: 85857
Item Type: Conference Paper
Refereed: Yes
Keywords: Brain structure, DTI, Genetics, Multiple comparisons corrections, Multivariate analysis, Voxel-based
DOI: 10.1109/ISBI.2014.6867881
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 IEEE
Deposited On: 09 Oct 2015 01:32
Last Modified: 21 Oct 2015 04:35

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