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

Authors
Kim, Hang-RaiJung, Sang-HyukKim, JaehoJang, HyeminKang, Sung HoonHwangbo, SongKim, Jun PyoKim, So YeonKim, BeomsuKim, SoyeonJeong, Jee HyangYoon, Soo JinPark, Kyung WonKim, Eun-JooYoon, BoraJang, Jae-WonHong, Jin YongChoi, Seong HyeNoh, YoungKim, Ko WoonKim, Si EunLee, Jin SanJung, Na-YeonLee, JuyounKim, Byeong C.Son, Sang JoonHong, Chang HyungNa, Duk L.Seo, Sang WonWon, Hong-HeeKim, Hee Jin
Issue Date
21-6월-2021
Publisher
BMC
Keywords
Alzheimer' s disease; Amyloid-beta; Genome-wide association studies; Positron emission tomography
Citation
ALZHEIMERS RESEARCH & THERAPY, v.13, no.1
Indexed
SCIE
SCOPUS
Journal Title
ALZHEIMERS RESEARCH & THERAPY
Volume
13
Number
1
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/139026
DOI
10.1186/s13195-021-00854-z
ISSN
1758-9193
Abstract
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 beta (A beta) 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 A beta positivity (measured by amyloid positron emission tomography). A beta 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 A beta 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 A beta 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 x 10(-8)). Prediction performance for A beta 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 A beta positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations.
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