Literature DB >> 24505811

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, Paul M Thompson1.   

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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Year:  2013        PMID: 24505811      PMCID: PMC4109883          DOI: 10.1007/978-3-642-40760-4_75

Source DB:  PubMed          Journal:  Med Image Comput Comput Assist Interv


  21 in total

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