Strategies for multivariate analyses of imaging genetics study in Alzheimer's disease

Alzheimer's disease (AD) is an incurable neurodegenerative disease primarily affecting the elderly population. Early diagnosis of AD is critical for the management of this disease. Imaging genetics examines the influence of genetic variants (i.e., single nucleotide polymorphisms (SNPs)) on brain structure and function and many novel approaches of imaging genetics are proposed for studying AD. We review and synthesize the Alzheimer's Disease Neuroimaging Initiative (ADNI) genetic associations with quantitative disease endophenotypes including structural and functional neuroimaging, diffusion tensor imaging (DTI), positron emission tomography (PET), and fluid biomarker assays. In this review, we survey recent publications using neuroimaging and genetic data of AD, with a focus on methods capturing multivariate effects accommodating the large number variables from both imaging data and genetic data. We review methods focused on bridging the imaging and genetic data by establishing genotype-phenotype association, including sparse canonical correlation analysis, parallel independent component analysis, sparse reduced rank regression, sparse partial least squares, genome-wide association study, and so on. The broad availability and wide scope of ADNI genetic and phenotypic data has advanced our understanding of the genetic basis of AD and has nominated novel targets for future pharmaceutical therapy and biomarker development.