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- 저자 : Joseph G. Ibrahim (검색결과 2 건)
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Bayesian bi-level variable selection for genome-wide survival study
Eunjee Lee,Joseph G. Ibrahim,Hongtu Zhu Korea Genome Organization 2023 Genomics & informatics Vol.21 No.3
Mild cognitive impairment (MCI) is a clinical syndrome characterized by the onset and evolution of cognitive impairments, often considered a transitional stage to Alzheimer's disease (AD). The genetic traits of MCI patients who experience a rapid progression to AD can enhance early diagnosis capabilities and facilitate drug discovery for AD. While a genome-wide association study (GWAS) is a standard tool for identifying single nucleotide polymorphisms (SNPs) related to a disease, it fails to detect SNPs with small effect sizes due to stringent control for multiple testing. Additionally, the method does not consider the group structures of SNPs, such as genes or linkage disequilibrium blocks, which can provide valuable insights into the genetic architecture. To address the limitations, we propose a Bayesian bi-level variable selection method that detects SNPs associated with time of conversion from MCI to AD. Our approach integrates group inclusion indicators into an accelerated failure time model to identify important SNP groups. Additionally, we employ data augmentation techniques to impute censored time values using a predictive posterior. We adapt Dirichlet-Laplace shrinkage priors to incorporate the group structure for SNP-level variable selection. In the simulation study, our method outperformed other competing methods regarding variable selection. The analysis of Alzheimer's Disease Neuroimaging Initiative (ADNI) data revealed several genes directly or indirectly related to AD, whereas a classical GWAS did not identify any significant SNPs.
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Jung, Jae-Hwan,Ji, Seong-Jin,Zhu, Hongtu,Ibrahim, Joseph G.,Fan, Yong,Lee, Eunjee The Korean Statistical Society 2020 Communications for statistical applications and me Vol.27 No.6
There is an emerging interest in brain functional connectivity (FC) based on functional Magnetic Resonance Imaging in Alzheimer's disease (AD) studies. The complex and high-dimensional structure of FC makes it challenging to explore the association between altered connectivity and AD susceptibility. We develop a pipeline to refine FC as proper covariates in a penalized logistic regression model and classify normal and AD susceptible groups. Three different quantification methods are proposed for FC refinement. One of the methods is dimension reduction based on common component analysis (CCA), which is employed to address the limitations of the other methods. We applied the proposed pipeline to the Alzheimer's Disease Neuroimaging Initiative (ADNI) data and deduced pathogenic FC biomarkers associated with AD susceptibility. The refined FC biomarkers were related to brain regions for cognition, stimuli processing, and sensorimotor skills. We also demonstrated that a model using CCA performed better than others in terms of classification performance and goodness-of-fit.
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