Transferability of Alzheimer Disease Polygenic Risk Score Across Populations and Its Association With Alzheimer Disease-Related Phenotypes

被引：21

作者：

Jung, Sang-Hyuk ^{[1
,2
]}

Kim, Hang-Rai ^{[3
]}

Chun, Min Young ^{[4
,5
]}

Jang, Hyemin ^{[4
,5
]}

Cho, Minyoung ^{[2
]}

Kim, Beomsu ^{[2
]}

Kim, Soyeon ^{[2
]}

Jeong, Jee Hyang ^{[6
]}

Yoon, Soo Jin ^{[7
]}

Park, Kyung Won ^{[8
]}

Kim, Eun-Joo ^{[9
,10
]}

Yoon, Bora ^{[11
]}

Jang, Jae-Won ^{[12
]}

Kim, Yeshin ^{[12
]}

Hong, Jin Yong ^{[13
]}

Choi, Seong Hye ^{[14
]}

Noh, Young ^{[15
]}

Kim, Ko Woon ^{[16
]}

Kim, Si Eun ^{[17
]}

Lee, Jin San ^{[18
]}

Jung, Na-Yeon ^{[10
,19
]}

Lee, Juyoun ^{[20
]}

Lee, Ae Young ^{[20
]}

Kim, Byeong C. ^{[21
]}

Cho, Soo Hyun ^{[21
]}

Cho, Hanna ^{[22
]}

Kim, Jong Hun ^{[23
]}

Jung, Young Hee ^{[24
]}

Lee, Dong Young ^{[25
]}

Lee, Jae-Hong ^{[26
]}

Lee, Eek-Sung ^{[27
]}

Kim, Seung Joo ^{[28
,29
]}

Moon, So Young ^{[30
]}

Son, Sang Joon ^{[31
]}

Hong, Chang Hyung ^{[31
]}

Bae, Jin-Sik ^{[32
]}

Lee, Sunghoon ^{[32
]}

Na, Duk L. ^{[4
,5
,33
]}

Seo, Sang Won ^{[2
,4
,5
,33
,34
]}

Cruchaga, Carlos ^{[35
,36
,37
]}

Kim, Hee Jin ^{[2
,4
,5
,33
]}

Won, Hong-Hee ^{[2
,33
,38
]}

机构：

[1] Univ Penn, Perelman Sch Med, Dept Biostat Epidemiol & Informat, Philadelphia, PA USA

[2] Sungkyunkwan Univ, Samsung Med Ctr, Samsung Adv Inst Hlth Sci & Technol, Dept Digital Hlth, Seoul, South Korea

[3] Dongguk Univ Ilsan Hosp, Dongguk Univ Coll Med, Dept Neurol, Goyang, South Korea

[4] Sungkyunkwan Univ, Samsung Med Ctr, Dept Neurol, Sch Med, Seoul, South Korea

[5] Samsung Med Ctr, Alzheimers Dis Convergence Res Ctr, Seoul, South Korea

[6] Ewha Womans Univ Sch Med, Ewha Womans Univ Seoul Hosp, Dept Neurol, Seoul, South Korea

[7] Eulji Univ, Eulji Univ Hosp, Dept Neurol, Sch Med, Daejeon, South Korea

[8] Dong A Univ, Grad Sch, Dept Translat Biomed Sci, Coll Med,Dept Neurol, Busan, South Korea

[9] Pusan Natl Univ, Pusan Natl Univ Hosp, Dept Neurol, Sch Med, Busan, South Korea

[10] Med Res Inst, Busan, South Korea

[11] Konyang Univ, Dept Neurol, Coll Med, Daejeon, South Korea

[12] Kangwon Natl Univ, Kangwon Natl Univ Hosp, Dept Neurol, Coll Med, Chunchon, South Korea

[13] Yonsei Univ, Dept Neurol, Wonju Coll Med, Wonju, South Korea

[14] Inha Univ, Dept Neurol, Sch Med, Incheon, South Korea

[15] Gachon Univ, Gil Med Ctr, Dept Neurol, Coll Med, Incheon, South Korea

[16] Jeonbuk Natl Univ Hosp, Sch Med, Dept Neurol, Jeonju, South Korea

[17] Inje Univ, Haeundae Paik Hosp, Dept Neurol, Coll Med, Busan, South Korea

[18] Kyung Hee Univ, Kyung Hee Univ Hosp, Dept Neurol, Coll Med, Seoul, South Korea

[19] Pusan Natl Univ, Sch Med, Dept Neurol, Yangsan Hosp, Busan, South Korea

[20] Chungnam Natl Univ Hosp, Dept Neurol, Daejeon, South Korea

[21] Chonnam Natl Univ, Dept Neurol, Sch Med, Gwangju, South Korea

[22] Yonsei Univ, Gangnam Severance Hosp, Dept Neurol, Coll Med, Seoul, South Korea

[23] Natl Hlth Insurance Serv Ilsan Hosp, Dept Neurol, Goyang, South Korea

[24] Hanyang Univ, Myongji Hosp, Dept Neurol, Goyang, South Korea

[25] Seoul Natl Univ Hosp, Dept Psychiat, Seoul, South Korea

[26] Univ Ulsan, Asan Med Ctr, Dept Neurol, Coll Med, Seoul, South Korea

[27] Soonchunhyang Univ, Dept Neurol, Bucheon Hosp, Bucheon, South Korea

[28] Gyeongsang Natl Univ, Dept Neurol, Sch Med, Chang Won, South Korea

[29] Gyeongsang Natl Univ, Changwon Hosp, Chang Won, South Korea

[30] Ajou Univ, Dept Neurol, Sch Med, Suwon, South Korea

[31] Ajou Univ, Dept Psychiat, Sch Med, Suwon, South Korea

[32] Eone Diagn Genome Ctr EDGC, Incheon, South Korea

[33] Sungkyunkwan Univ, Dept Hlth Sci & Technol, SAIHST, Seoul, South Korea

[34] Sungkyunkwan Univ, Dept Intelligent Precis Healthcare Convergence, Seoul, South Korea

[35] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[36] Washington Univ, NeuroGen & Informat Ctr, Sch Med, St Louis, MO USA

[37] Washington Univ, Sch Med, Charles F & Joanne Knight Alzheimer Dis Res Ctr, St Louis, MO USA

[38] Samsung Med Ctr, Samsung Genome Inst, Seoul, South Korea

来源：

JAMA NETWORK OPEN | 2022年 / 5卷 / 12期

基金：

新加坡国家研究基金会;

关键词：

DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; HAZARD SCORE; DEMENTIA; RECOMMENDATIONS; METAANALYSIS; WORKGROUPS; PREDICTION; TAU;

D O I：

10.1001/jamanetworkopen.2022.47162

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 beta deposition (A beta). 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 e4 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 A beta deposition independent of APOE e4 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.

引用

页数：13

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