한빛사논문
- 조회386
Sang-Hyuk Jung, PhD1,2; Hang-Rai Kim, MD, PhD3; Min Young Chun, MD, PhD4,5; Hyemin Jang, MD, PhD4,5; Minyoung Cho, MS2; Beomsu Kim, BS2; Soyeon Kim, PhD2; Jee Hyang Jeong, MD, PhD6; Soo Jin Yoon, MD, PhD7; Kyung Won Park, MD, PhD8; Eun-Joo Kim, MD, PhD9; Bora Yoon, MD, PhD10; Jae-Won Jang, MD, PhD11; Yeshin Kim, MD, PhD11; Jin Yong Hong, MD, PhD12; Seong Hye Choi, MD, PhD13; Young Noh, MD, PhD14; Ko Woon Kim, MD, PhD15; Si Eun Kim, MD16; Jin San Lee, MD, PhD17; Na-Yeon Jung, MD, PhD18; Juyoun Lee, MD, PhD19; Ae Young Lee, MD, PhD19; Byeong C. Kim, MD, PhD20; Soo Hyun Cho, MD, PhD20; Hanna Cho, MD, PhD21; Jong Hun Kim, MD, PhD22; Young Hee Jung, MD, PhD23; Dong Young Lee, MD, PhD24; Jae-Hong Lee, MD, PhD25; Eek-Sung Lee, MD, PhD26; Seung Joo Kim, MD27; So Young Moon, MD, PhD28; Sang Joon Son, MD, PhD29; Chang Hyung Hong, MD, PhD29; Jin-Sik Bae, PhD30; Sunghoon Lee, PhD30; Duk L. Na, MD, PhD4,5,31; Sang Won Seo, MD, PhD2,4,5,31,32; Carlos Cruchaga, PhD33,34,35; Hee Jin Kim, MD, PhD2,4,5,31; Hong-Hee Won, PhD2,31,36
1Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
2Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea
3Department of Neurology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea
4Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
5Alzheimer’s Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea
6Department of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea
7Department of Neurology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Republic of Korea
8Department of Neurology, Dong-A University College of Medicine, Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan, Republic of Korea
9Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, Republic of Korea
10Department of Neurology, Konyang University College of Medicine, Daejeon, Republic of Korea
11Department of Neurology, Kangwon National University Hospital, Kangwon National University College of Medicine, Chuncheon, Republic of Korea
12Department of Neurology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
13Department of Neurology, Inha University School of Medicine, Incheon, Republic of Korea
14Department of Neurology, Gachon University College of Medicine, Gil Medical Center, Incheon, Republic of Korea
15Department of Neurology, School of Medicine, Jeonbuk National University Hospital, Jeonju, Republic of Korea
16Department of Neurology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea
17Department of Neurology, Kyung Hee University College of Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea
18Department of Neurology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, Republic of Korea
19Department of Neurology, Chungnam National University Hospital, Daejeon, Republic of Korea
20Departmet of Neurology, Chonnam National University School of Medicine, Gwangju, Republic of Korea
21Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
22Department of Neurology, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea
23Department of Neurology, Myongji Hospital, Hanyang University, Goyang, Republic of Korea
24Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea
25Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
26Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
27Department of Neurology, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
28Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea
29Department of Psychiatry, Ajou University School of Medicine, Suwon, Republic of Korea
30Eone-Diagnomics Genome Center (EDGC), Incheon, Republic of Korea
31Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
32Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Seoul, Republic of Korea
33Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri
34NeuroGenomics and Informatics Center, Washington University School of Medicine, St Louis, Missouri
35The Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, Missouri
36Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea
Drs S.-H. Jung, and H.-R. Kim contributed equally to this work as cofirst authors.
Corresponding Author: Hee Jin Kim, MD, PhD, and Hong-Hee Won, PhD
Abstract
Importance Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry.
Objective To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations.
Design, Setting, and Participants This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21 982 AD cases and 41 944 controls). This PRS was tested for an association with AD dementia and its related phenotypes in 1634 Korean individuals, who were recruited from 2013 to 2019. The association of a PRS based on a GWAS of a Japanese population (the National Center for Geriatrics and Gerontology; 3962 AD cases and 4074 controls) and a transancestry meta-analysis of European and Japanese GWASs was also evaluated. Data were analyzed from December 2020 to June 2021.
Main Outcomes and Measures Risk of AD dementia, amnestic mild cognitive impairment (aMCI), earlier symptom onset, and amyloid β deposition (Aβ).
Results A total of 1634 Korean patients (969 women [59.3%]), including 716 individuals (43.6%) with AD dementia, 222 (13.6%) with aMCI, and 699 (42.8%) cognitively unimpaired controls, were analyzed in this study. The mean (SD) age of the participants was 71.6 (9.0) years. Higher PRS was associated with a higher risk of AD dementia independent of APOE ɛ4 status in the Korean population (OR, 1.95; 95% CI, 1.40-2.72; P < .001). Furthermore, PRS was associated with aMCI, earlier symptom onset, and Aβ deposition independent of APOE ɛ4 status. The PRS based on a transancestry meta-analysis of data sets comprising 2 distinct ancestries showed a slightly improved accuracy.
Conclusions and Relevance In this cohort study, a PRS derived from a European GWAS identified individuals at a high risk for AD dementia in the Korean population. These findings emphasize the transancestry transferability and clinical value of PRSs and suggest the importance of enriching diversity in genetic studies of AD.
논문정보
- Research article
- 2022년 12월 (BRIC 등록일 2022-12-19)
- 국내(교신)+국외 연구진
- 의약학 > 유전 및 유전체의학
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