한빛사논문
Thea J Rosewood 1,2,3, Kwangsik Nho 1,2,4, Shannon L Risacher 1,3, Shiwei Liu 1,3, Sujuan Gao 1,5, Li Shen 6, Tatiana Foroud 1,2, Andrew J Saykin 1,2,3; Alzheimer's Disease Neuroimaging Initiative
1Indiana Alzheimer's Disease Research Center, Indianapolis, Indiana, USA.
2Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
3Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, USA.
4School of Informatics and Computing, Indiana University, Indianapolis, Indiana, USA.
5Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
6Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Correspondence : Andrew J. Saykin and Kwangsik Nho
Abstract
INTRODUCTION
The genetic pathways that influence longitudinal heterogeneous changes in Alzheimer's disease (AD) may provide insight into disease mechanisms and potential therapeutic targets.
METHODS
Longitudinal endophenotypes from the Alzheimer's Disease Neuroimaging Initiative (ADNI) representing amyloid, tau, neurodegeneration (A/T/N), and cognition were selected. Genome-wide association analysis was performed using a linear mixed model (LMM) approach, followed by gene and pathway enrichment with significant and functionally relevant SNPs.
RESULTS
A total of 33 and 19 statistically significant pathways were identified associating with the intercept and longitudinal trajectory, respectively. The longitudinal intercept pathways represent eight groups: immune, metabolic, cell growth and survival, DNA maintenance, neuronal signaling, RAS/MAPK/ERK signaling pathways, vesicle and lysosomal transport, and transcription modification. Longitudinal trajectory pathways represented six groups: Immune, metabolic, cell signaling, cytoskeleton, and glycosylation.
DISCUSSION
Longitudinal enrichment identified pathways that uniquely associate with trajectories of key AD biomarkers and cognition, providing new insight into AD course-related mechanisms and potential new therapeutic targets.
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