title: Exhaustive search of the SNP-sNP interactome identifies epistatic effects on brain volume in two cohorts.
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.
authors: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, USA.
authors: Derrek P
authors: DP
authors: Hibar
authors: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, USA.
authors: Jason L
authors: JL
authors: Stein
authors: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, USA.
authors: Neda
authors: N
authors: Jahanshad
authors: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, USA.
authors: Omid
authors: O
authors: Kohannim
authors: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, USA.
authors: Arthur W
authors: AW
authors: Toga
authors: Center for Magnetic Resonance, School of Psychology, University of Queensland, Brisbane, Australia.
authors: Katie L
authors: KL
authors: McMahon
authors: Functional Magnetic Resonance Imaging Laboratory, School of Psychology, University of Queensland, Brisbane, Australia.
authors: Greig I
authors: GI
authors: de Zubicaray
authors: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
authors: Grant W
authors: GW
authors: Montgomery
authors: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
authors: Nicholas G
authors: NG
authors: Martin
authors: Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
authors: Margaret J
authors: MJ
authors: Wright
authors: Department of Radiology, UC San Francisco, San Francisco, USA.
authors: Michael W
authors: MW
authors: Weiner
authors: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, USA.
authors: Paul M
authors: PM
authors: Thompson
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002874:Chromosome Mapping / Q000379:methods*; D015331:Cohort Studies; D063132:Connectome / Q000379:methods*; D004843:Epistasis, Genetic / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*