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

Sang Hyuk Jung, Hang Rai Kim, Min Young Chun, Hyemin Jang, Minyoung Cho, Beomsu Kim, Soyeon Kim, Jee Hyang Jeong, Soo Jin Yoon, Kyung Won Park, Eun Joo Kim, Bora Yoon, Jae Won Jang, Yeshin Kim, Jin Yong Hong, Seong Hye Choi, Young Noh, Ko Woon Kim, Si Eun Kim, Jin San LeeNa Yeon Jung, Juyoun Lee, Ae Young Lee, Byeong C. Kim, Soo Hyun Cho, Hanna Cho, Jong Hun Kim, Young Hee Jung, Dong Young Lee, Jae Hong Lee, Eek Sung Lee, Seung Joo Kim, So Young Moon, Sang Joon Son, Chang Hyung Hong, Jin Sik Bae, Sunghoon Lee, Duk L. Na, Sang Won Seo, Carlos Cruchaga, Hee Jin Kim, Hong Hee Won

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10 Scopus citations


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; 21982 AD cases and 41944 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 ϵ4 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 ϵ4 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.

Original languageEnglish
Pages (from-to)E2247162
JournalJAMA network open
Issue number12
StatePublished - 15 Dec 2022

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