Identifying novel genetic variants for brain amyloid deposition: a genome-wide association study in the Korean population

Hang Rai Kim, Sang Hyuk Jung, Jaeho Kim, Hyemin Jang, Sung Hoon Kang, Song Hwangbo, Jun Pyo Kim, So Yeon Kim, Beomsu Kim, Soyeon Kim, Jee Hyang Jeong, Soo Jin Yoon, Kyung Won Park, Eun Joo Kim, Bora Yoon, Jae Won Jang, Jin Yong Hong, Seong Hye Choi, Young Noh, Ko Woon KimSi Eun Kim, Jin San Lee, Na Yeon Jung, Juyoun Lee, Byeong C. Kim, Sang Joon Son, Chang Hyung Hong, Duk L. Na, Sang Won Seo, Hong Hee Won, Hee Jin Kim

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7 Scopus citations


Background: Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer’s disease (AD). However, most GWAS were conducted in individuals of European ancestry, and non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid β (Aβ) positivity using a large sample of Korean population. Methods: One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired [CU], 330 with amnestic mild cognitive impairment [aMCI], and 477 with AD dementia [ADD]) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aβ positivity (measured by amyloid positron emission tomography). Aβ prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs. Results: In addition to APOE, we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aβ positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aβ positivity (p < 0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level (p < 5.0 × 10−8). Prediction performance for Aβ positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74–0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain. Conclusion: The novel genetic variants associated with FGL2 decreased risk of Aβ positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations.

Original languageEnglish
Article number117
JournalAlzheimer's Research and Therapy
Issue number1
StatePublished - Dec 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).


  • Alzheimer’s disease
  • Amyloid-beta
  • Genome-wide association studies
  • Positron emission tomography


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