title: Genetic clustering on the hippocampal surface for genome-wide association studies.
abstract: Imaging genetics aims to discover how variants in the human genome influence brain measures derived from images. Genome-wide association scans (GWAS) can screen the genome for common differences in our DNA that relate to brain measures. In small samples, GWAS has low power as individual gene effects are weak and one must also correct for multiple comparisons across the genome and the image. Here we extend recent work on genetic clustering of images, to analyze surface-based models of anatomy using GWAS. We performed spherical harmonic analysis of hippocampal surfaces, automatically extracted from brain MRI scans of 1254 subjects. We clustered hippocampal surface regions with common genetic influences by examining genetic correlations (r(g)) between the normalized deformation values at all pairs of surface points. Using genetic correlations to cluster surface measures, we were able to boost effect sizes for genetic associations, compared to clustering with traditional phenotypic correlations using Pearson's r.
authors.affiliation: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Derrek P
authors.initials: DP
authors.lastname: Hibar
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Medland
authors.affiliation: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Stein
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Sungeun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saykin
authors.affiliation: Functional Magnetic Resonance Imaging Laboratory, School of Psychology, University of Queensland, Brisbane, Australia.
authors.forename: Greig I
authors.initials: GI
authors.lastname: de Zubicaray
authors.affiliation: Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Katie L
authors.initials: KL
authors.lastname: McMahon
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.affiliation: KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Agartz
authors.affiliation: KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D060825:Cognitive Dysfunction / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity