한빛사논문
- 조회248
Jaeyoon Chung 1, Anjali Das 2, Xinyu Sun 1, Débora R Sobreira 3, Yuk Yee Leung 4, Catherine Igartua 2, Sahar Mozaffari 2, Yi-Fan Chou 4, Sam Thiagalingam 1, Jesse Mez 5, Xiaoling Zhang 1, Gyungah R Jun 1 6 7, Thor D Stein 8, Brian W Kunkle 9, Eden R Martin 9, Margaret A Pericak-Vance 9, Richard Mayeux 10, Jonathan L Haines 11, Gerard D Schellenberg 4, Marcelo A Nobrega 2, Kathryn L Lunetta 7, Jayant M Pinto 3, Li-San Wang 4, Carole Ober 2, Lindsay A Farrer 1 5 6 7 12
1Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts, USA.
2Department of Human Genetics, The University of Chicago, Chicago, Illinois, USA.
3Department of Surgery/Section of Otolaryngology-Head and Neck Surgery, The University of Chicago, Chicago, Illinois, USA.
4Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
5Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
6Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, USA.
7Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
8Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
9Dr. John T. Macdonald Foundation of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
10Department of Neurology, Columbia University, New York City, New York, USA.
11Department of Population and Quantitative Health Sciences and Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.
12Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA.
CORRESPONDING AUTHOR: Lindsay A. Farrer
Abstract
Introduction: Variants in the tau gene (MAPT) region are associated with breast cancer in women and Alzheimer's disease (AD) among persons lacking apolipoprotein E ε4 (ε4-).
Methods: To identify novel genes associated with tau-related pathology, we conducted two genome-wide association studies (GWAS) for AD, one among 10,340 ε4- women in the Alzheimer's Disease Genetics Consortium (ADGC) and another in 31 members (22 women) of a consanguineous Hutterite kindred.
Results: We identified novel associations of AD with MGMT variants in the ADGC (rs12775171, odds ratio [OR] = 1.4, P = 4.9 × 10-8 ) and Hutterite (rs12256016 and rs2803456, OR = 2.0, P = 1.9 × 10-14 ) datasets. Multi-omics analyses showed that the most significant and largest number of associations among the single nucleotide polymorphisms (SNPs), DNA-methylated CpGs, MGMT expression, and AD-related neuropathological traits were observed among women. Furthermore, promoter capture Hi-C analyses revealed long-range interactions of the MGMT promoter with MGMT SNPs and CpG sites.
Discussion: These findings suggest that epigenetically regulated MGMT expression is involved in AD pathogenesis, especially in women.
논문정보
- Research article
- 2022년 06월 (BRIC 등록일 2023-01-05)
- 국외 연구진
- 생명과학 > 유전학
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