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Exhaustive Search of the SNP-SNP Interactome Identifies Epistatic Effects on Brain Volume in Two Cohorts
Derrek P. Hibar1, Jason L. Stein1, Neda Jahanshad1, Omid Kohannim1, Arthur W. Toga1, Katie L. McMahon2, Greig I. de Zubicaray3, Grant W. Montgomery4, Nicholas G. Martin4, Margaret J. Wright4, Michael W. Weiner5, 6, and Paul M. Thompson1
1Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, USA
2Center for Magnetic Resonance, School of Psychology, University of Queensland, Brisbane, Australia
3Functional Magnetic Resonance Imaging Laboratory, School of Psychology, University of Queensland, Brisbane, Australia
4Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia
5Departments of Radiology, Medicine, Psychiatry, UC San Francisco, San Francisco, USA
6Department of Veterans Affairs Medical Center, San Francisco, USA
Abstract. The SNP-SNP interactome has rarely been explored in the context of neuroimaging genetics mainly due to the complexity of conducting ~1011 pairwise statistical tests. However, recent advances in machine learning, specifically the iterative sure independence screening (SIS) method, have enabled the analysis of datasets where the number of predictors is much larger than the number of observations. Using an implementation of the SIS algorithm (called EPISIS), we used exhaustive search of the genome-wide, SNP-SNP interactome to identify and prioritize SNPs for interaction analysis. We identified a significant SNP pair, rs1345203 and rs1213205, associated with temporal lobe volume. We further examined the full-brain, voxelwise effects of the interaction in the ADNI dataset and separately in an independent dataset of healthy twins (QTIM). We found that each additional loading in the epistatic effect was associated with ~5% greater brain regional brain volume (a protective effect) in both the ADNI and QTIM samples.
Keywords: epistasis, interaction, genome, sure independence, tensor-based morphometry
LNCS 8151, p. 600 ff.
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© Springer-Verlag Berlin Heidelberg 2013