Browsing by Author "Jeong, Jee Hyang"

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    APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer's Disease Risk in a Multiracial Sample
    (MDPI, 2019-08-16) Choi, Kyu Yeong; Lee, Jang Jae; Gunasekaran, Tamil Iniyan; Kang, Sarang; Lee, Wooje; Jeong, Jangho; Lim, Ho Jae; Zhang, Xiaoling; Zhu, Congcong; Won, So-Yoon; Choi, Yu Yong; Seo, Eun Hyun; Lee, Seok Cheol; Gim, Jungsoo; Chung, Ji Yeon; Chong, Ari; Byun, Min Soo; Seo, Sujin; Ko, Pan-Woo; Han, Ji-Won; McLean, Catriona; Farrell, John; Lunetta, Kathryn L.; Miyashita, Akinori; Hara, Norikazu; Won, Sungho; Choi, Seong-Min; Ha, Jung-Min; Jeong, Jee Hyang; Kuwano, Ryozo; Song, Min Kyung; An, Seong Soo A.; Lee, Young Min; Park, Kyung Won; Lee, Ho-Won; Choi, Seong Hye; Rhee, Sangmyung; Song, Woo Keun; Lee, Jung Sup; Mayeux, Richard; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Choo, IL Han; Nho, Kwangsik; Kim, Ki-Woong; Lee, Dong Young; Kim, SangYun; Kim, Byeong C.; Kim, Hoowon; Jun, Gyungah R.; Schellenberg, Gerard D.; Ikeuchi, Takeshi; Farrer, Lindsay A.; Lee, Kun Ho; Radiology and Imaging Sciences, School of Medicine
    Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10-94; GT: OR = 15.87, p = 2.62 × 10-9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10-108; GT: OR = 12.63, p = 3.44 × 10-64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.
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    Distinctive Temporal Trajectories of Alzheimer's Disease Biomarkers According to Sex and APOE Genotype: Importance of Striatal Amyloid
    (Frontiers Media, 2022-02-07) Kim, Jun Pyo; Chun, Min Young; Kim, Soo-Jon; Jang, Hyemin; Kim, Hee Jin; Jeong, Jee Hyang; Na, Duk L.; Seo, Sang Won; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
    Purpose: Previously, sex and apolipoprotein E (APOE) genotype had distinct effects on the cognitive trajectory across the Alzheimer's disease (AD) continuum. We therefore aimed to investigate whether these trajectory curves including β-amyloid (Aβ) accumulation in the cortex and striatum, and tau accumulation would differ according to sex and APOE genotype. Methods: We obtained 534 subjects for 18F-florbetapir (AV45) PET analysis and 163 subjects for 18F-flortaucipir (AV1451) PET analysis from the Alzheimer's Disease Neuroimaging Initiative database. For cortical Aβ, striatal Aβ, and tau SUVR, we fitted penalized splines to model the slopes of SUVR value as a non-linear function of baseline SUVR value. By integrating the fitted splines, we obtained the predicted SUVR curves as a function of time. Results: The time from initial SUVR to the cutoff values were 14.9 years for cortical Aβ, 18.2 years for striatal Aβ, and 22.7 years for tau. Although there was no difference in cortical Aβ accumulation rate between women and men, striatal Aβ accumulation was found to be faster in women than in men, and this temporal difference according to sex was more pronounced in tau accumulation. However, APOE ε4 carriers showed faster progression than non-carriers regardless of kinds of AD biomarkers' trajectories. Conclusion: Our temporal trajectory models illustrate that there is a distinct progression pattern of AD biomarkers depending on sex and APOE genotype. In this regard, our models will be able to contribute to designing personalized treatment and prevention strategies for AD in clinical practice.
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    Identifying novel genetic variants for brain amyloid deposition: a genome-wide association study in the Korean population
    (BMC, 2021-06-21) Kim, Hang-Rai; Jung, Sang-Hyuk; Kim, Jaeho; Jang, Hyemin; Kang, Sung Hoon; Hwangbo, Song; Kim, Jun Pyo; Kim, So Yeon; Kim, Beomsu; Kim, Soyeon; Jeong, Jee Hyang; Yoon, Soo Jin; Park, Kyung Won; Kim, Eun-Joo; Yoon, Bora; Jang, Jae-Won; Hong, Jin Yong; Choi, Seong Hye; Noh, Young; Kim, Ko Woon; Kim, Si Eun; Lee, Jin San; Jung, Na-Yeon; Lee, Juyoun; Kim, Byeong C.; Son, Sang Joon; Hong, Chang Hyung; Na, Duk L.; Seo, Sang Won; Won, Hong-Hee; Kim, Hee Jin; Radiology and Imaging Sciences, School of Medicine
    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.