title: Mining Outcome-relevant Brain Imaging Genetic Associations via Three-way Sparse Canonical Correlation Analysis in Alzheimer's Disease.
abstract: Neuroimaging genetics is an emerging field that aims to identify the associations between genetic variants (e.g., single nucleotide polymorphisms (SNPs)) and quantitative traits (QTs) such as brain imaging phenotypes. In recent studies, in order to detect complex multi-SNP-multi-QT associations, bi-multivariate techniques such as various structured sparse canonical correlation analysis (SCCA) algorithms have been proposed and used in imaging genetics studies. However, associations between genetic markers and imaging QTs identified by existing bi-multivariate methods may not be all disease specific. To bridge this gap, we propose an analytical framework, based on three-way sparse canonical correlation analysis (T-SCCA), to explore the intrinsic associations among genetic markers, imaging QTs, and clinical scores of interest. We perform an empirical study using the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to discover the relationships among SNPs from AD risk gene APOE, imaging QTs extracted from structural magnetic resonance imaging scans, and cognitive and diagnostic outcomes. The proposed T-SCCA model not only outperforms the traditional SCCA method in terms of identifying strong associations, but also discovers robust outcome-relevant imaging genetic patterns, demonstrating its promise for improving disease-related mechanistic understanding.
authors.affiliation: College of Computer Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Hao
authors.affiliation: College of Computer Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.
authors.forename: Chanxiu
authors.initials: C
authors.lastname: Li
authors.affiliation: School of Automation, Northwestern Polytechnical University, Xi'an 710072, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Radiology and Imaging Sciences, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Radiology and Imaging Sciences, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.|School of Informatics and Computing, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Radiology and Imaging Sciences, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Risacher
authors.affiliation: Department of Radiology and Imaging Sciences, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saykin
authors.affiliation: Department of Radiology and Imaging Sciences, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: College of Computer Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.
authors.forename: Daoqiang
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D015331:Cohort Studies; D057225:Data Mining; D066264:Datasets as Topic; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D015999:Multivariate Analysis; D059906:Neuroimaging; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index
chemical_list: D001057:Apolipoproteins E