Exhaustive search of the SNP-sNP interactome identifies epistatic effects on brain volume in two cohorts

Hibar, D. P., Stein, J. L., Jahanshad, N., Kohannim, O., Toga, A. W., McMahon, K. L., de Zubicaray, G. I., Montgomery, G. W., Martin, N. G., Wright, M. J., Weiner, M. W., & Thompson, P. M. (2013) Exhaustive search of the SNP-sNP interactome identifies epistatic effects on brain volume in two cohorts. In Kensaku, Mori, Sakuma, Ichiro, Sato, Yoshinobu, Barillot, Christian, & Navab, Nassir (Eds.) Medical Image Computing and Computer-Assisted Intervention – MICCAI 2013: 16th International Conference, Nagoya, Japan, September 22-26, 2013, Proceedings, Part III, Springer Berlin Heidelberg, Nagoya, Japan, pp. 600-607.

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Abstract

The SNP-SNP interactome has rarely been explored in the context of neuroimaging genetics mainly due to the complexity of conducting approximately 10(11) 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 approximately 5% greater brain regional brain volume (a protective effect) in both the ADNI and QTIM samples.

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ID Code: 85768
Item Type: Conference Paper
Refereed: Yes
DOI: 10.1007/978-3-642-40760-4_75
ISBN: 9783642407604
ISSN: 0302-9743
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2013 Springer-Verlag Berlin Heidelberg
Deposited On: 09 Oct 2015 03:01
Last Modified: 21 Oct 2015 02:35

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