title: Hippocampal surface mapping of genetic risk factors in AD via sparse learning models.
abstract: Genetic mapping of hippocampal shape, an under-explored area, has strong potential as a neurodegeneration biomarker for AD and MCI. This study investigates the genetic effects of top candidate single nucleotide polymorphisms (SNPs) on hippocampal shape features as quantitative traits (QTs) in a large cohort. FS+LDDMM was used to segment hippocampal surfaces from MRI scans and shape features were extracted after surface registration. Elastic net (EN) and sparse canonical correlation analysis (SCCA) were proposed to examine SNP-QT associations, and compared with multiple regression (MR). Although similar in power, EN yielded substantially fewer predictors than MR. Detailed surface mapping of global and localized genetic effects were identified by MR and EN to reveal multi-SNP-single-QT relationships, and by SCCA to discover multi-SNP-multi-QT associations. Shape analysis identified stronger SNP-QT correlations than volume analysis. Sparse multivariate models have greater power to reveal complex SNP-QT relationships. Genetic analysis of quantitative shape features has considerable potential for enhancing mechanistic understanding of complex disorders like AD.
authors: Radiology and Imaging Sciences, Indiana University School of Medicine, IN, USA. wanjing@iupui.edu
authors: Jing
authors: J
authors: Wan
authors: Sungeun
authors: S
authors: Kim
authors: Mark
authors: M
authors: Inlow
authors: Kwangsik
authors: K
authors: Nho
authors: Shanker
authors: S
authors: Swaminathan
authors: Shannon L
authors: SL
authors: Risacher
authors: Shiaofen
authors: S
authors: Fang
authors: Michael W
authors: MW
authors: Weiner
authors: M Faisal
authors: MF
authors: Beg
authors: Lei
authors: L
authors: Wang
authors: Andrew J
authors: AJ
authors: Saykin
authors: Li
authors: L
authors: Shen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007858:Learning; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D008959:Models, Neurological; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012307:Risk Factors