한빛사논문
- 조회172
Jaeyoon Chung 1, Nathan Sahelijo 1, Toru Maruyama 2, Junming Hu 1, Rebecca Panitch 1, Weiming Xia 3,4, Jesse Mez 5, Thor D Stein 4,6,7; Alzheimer's Disease Neuroimaging Initiative 1; Andrew J Saykin 8,9, Haruko Takeyama 2,10,11,12, Lindsay A Farrer 1,5,13,14,15, Paul K Crane 16, Kwangsik Nho 8,9, Gyungah R Jun 1,13,14
1Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts, USA.
2Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan.
3Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA.
4Department of Veterans Affairs Medical Center, Bedford, Massachusetts, USA.
5Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
6Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
7Boston VA Healthcare Center, Boston, Massachusetts, USA.
8Department of Radiology and Imaging Sciences and Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
9Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
10Computational Bio Big-Data Open Innovation Laboratory, AIST-Waseda University, Tokyo, Japan.
11Research Organization for Nano and Life Innovations, Waseda University, Tokyo, Japan.
12Institute for Advanced Research of Biosystem Dynamics, Waseda Research Institute for Science and Engineering, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
13Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, USA.
14Departments of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
15Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA.
16Department of Medicine, University of Washington, Seattle, Washington, USA.
CORRESPONDING AUTHOR : Gyungah R. Jun
Abstract
Introduction: Alzheimer's disease (AD) is heterogeneous, both clinically and neuropathologically. We investigated whether polygenic risk scores (PRSs) integrated with transcriptome profiles from AD brains can explain AD clinical heterogeneity.
Methods: We conducted co-expression network analysis and identified gene sets (modules) that were preserved in three AD transcriptome datasets and associated with AD-related neuropathological traits including neuritic plaques (NPs) and neurofibrillary tangles (NFTs). We computed the module-based PRSs (mbPRSs) for each module and tested associations with mbPRSs for cognitive test scores, cognitively defined AD subgroups, and brain imaging data.
Results: Of the modules significantly associated with NPs and/or NFTs, the mbPRSs from two modules (M6 and M9) showed distinct associations with language and visuospatial functioning, respectively. They matched clinical subtypes and brain atrophy at specific regions.
Discussion: Our findings demonstrate that polygenic profiling based on co-expressed gene sets can explain heterogeneity in AD patients, enabling genetically informed patient stratification and precision medicine in AD.
Highlights: Co-expression gene-network analysis in Alzheimer's disease (AD) brains identified gene sets (modules) associated with AD heterogeneity. AD-associated modules were selected when genes in each module were enriched for neuritic plaques and neurofibrillary tangles. Polygenic risk scores from two selected modules were linked to the matching cognitively defined AD subgroups (language and visuospatial subgroups). Polygenic risk scores from the two modules were associated with cognitive performance in language and visuospatial domains and the associations were confirmed in regional-specific brain atrophy data.
논문정보
- Research article
- 2023년 05월 (BRIC 등록일 2023-06-02)
- 국외 연구진
- 생명과학 > 유전학
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