Browsing by Author "Kang, Sung Hoon"

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    Differential effects of risk factors on the cognitive trajectory of early- and late-onset Alzheimer’s disease
    (BMC, 2021-06-14) Kim, Jaeho; Woo, Sook-Young; Kim, Seonwoo; Jang, Hyemin; Kim, Junpyo; Kim, Jisun; Kang, Sung Hoon; Na, Duk L.; Chin, Juhee; Apostolova, Liana G.; Seo, Sang Won; Kim, Hee Jin; Neurology, School of Medicine
    Background: Although few studies have shown that risk factors for Alzheimer's disease (AD) are associated with cognitive decline in AD, not much is known whether the impact of risk factors differs between early-onset AD (EOAD, symptom onset < 65 years of age) versus late-onset AD (LOAD). Therefore, we evaluated whether the impact of Alzheimer's disease (AD) risk factors on cognitive trajectories differ in EOAD and LOAD. Methods: We followed-up 193 EOAD and 476 LOAD patients without known autosomal dominant AD mutation for 32.3 ± 23.2 months. Mixed-effects model analyses were performed to evaluate the effects of APOE ε4, low education, hypertension, diabetes, dyslipidemia, and obesity on cognitive trajectories. Results: APOE ε4 carriers showed slower cognitive decline in general cognitive function, language, and memory domains than APOE ε4 carriers in EOAD but not in LOAD. Although patients with low education showed slower cognitive decline than patients with high education in both EOAD and LOAD, the effect was stronger in EOAD, specifically in frontal-executive function. Patients with hypertension showed faster cognitive decline than did patients without hypertension in frontal-executive and general cognitive function in LOAD but not in EOAD. Patients with obesity showed slower decline in general cognitive function than non-obese patients in EOAD but not in LOAD. Conclusions: Known risk factors for AD were associated with slower cognitive decline in EOAD but rapid cognitive decline in LOAD.
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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.