한빛사논문
- 조회315
Jun Pyo Kima,b, Bo-Hyun Kimc, Paula J. Bicea,f, Sang Won Seod, David A. Bennette, Andrew J. Saykina,f,g, Kwangsik Nhoa,f,h,*
aCenter for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana
bMedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea
cDepartment of Biomedical Engineering, Hanyang University, Seoul, Korea
dDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
eRush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois
fIndiana Alzheimer’s Disease Research Center, Indiana University School of Medicine, Indianapolis, Indiana
gDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana
hCenter for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana
*Corresponding author.
Abstract
Background
DNA methylation is a key epigenetic marker, and its alternations may be involved in Alzheimer’s disease (AD). CpGs sharing similar biological functions or pathways tend to be co-methylated.
Methods
We performed an integrative network-based DNA methylation analysis on 2 independent cohorts (N = 941) using brain DNA methylation profiles and RNA-sequencing as well as AD pathology data.
Results
Weighted co-methylation network analysis identified 6 modules as significantly associated with neuritic plaque burden. In total, 15 hub CpGs including 3 novel CpGs were identified and replicated as being significantly associated with AD pathology. Furthermore, we identified and replicated 4 target genes (ATP6V1G2, VCP, RAD52, and LST1) as significantly regulated by DNA methylation at hub CpGs. In particular, VCP gene expression was also associated with AD pathology in both cohorts.
Conclusions
This integrative network-based multiomics study provides compelling evidence for a potential role of DNA methylation alternations and their target genes in AD.
논문정보
- Research article
- 2022년 06월 (BRIC 등록일 2022-10-11)
- 국내+국외 연구진
- 의약학 > 인체시스템의학
관련 웨비나
![Co-methylation 네트워크를 이용한 알츠하이머병 병리 연관 멀티오믹스 (후성유전체, 전사체) 분석 연구[Biol. Psychiatry]](/upload/board/files/onseminar/thumb/thumb_0000463.png)
학술웨비나
Co-methylation 네트워크를 이용한 알츠하이머병 병리 연관 멀티오믹스 (후성유전체, 전사체) 분석 연구[Biol. Psychiatry] 알츠하이머병의 유전적 원인과 관련해서 많은 연구가 이루어져왔고 많은 연관 변이들이 밝혀져 왔습니다. 하지만 유전자형 만으로는 알츠차이머병의 유전적 요인의 일부만 설명이 가능하여 후성유전적 요인 및 유전자 발현과 관련한 연구들이 많이 이루어지고 있습니다. 이번 연구에서는 뇌 부검 샘플을 보유한 ROSMAP 및 MSBB 코호트의 DNA 메틸화 데이터에 Co-methylation network analysis 기법을 이용하여 새로운 메틸화 위치 및 연관 유전자를 발견하였습니다. 추가로 연관된 유전자 발현을 RNA 데이터를 통하여 찾아냈습니다. 이번 세미나에서 후성유전체 및 전사체 데이터를 통하여 알츠하이머병의 밝혀지지 않은 유전학적 요인들에 더 접근할 수 있는 가능성을 보여드리고자 합니다. Alzheimer’s disease, DNA methylation, Multiomics- 김준표(Indiana University)
댓글 작성 로그인
팝업 닫기관련 링크
연구자 ID
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
