Clinical effects of novel susceptibility genes for beta-amyloid: a gene-based association study in the Korean population
Amyloid-beta (Aβ) is a pathological hallmark of Alzheimer’s disease (AD). We aimed to identify genes related to Aβ uptake in the Korean population and investigate the effects of these novel genes on clinical outcomes, including neurodegeneration and cognitive impairments. We recruited a total of 759...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1278998/full |
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| author | Bo-Hyun Kim HyunWoo Lee Hongki Ham Hongki Ham Hee Jin Kim Hee Jin Kim Hee Jin Kim Hyemin Jang Hyemin Jang Hyemin Jang Hyemin Jang Jun Pyo Kim Jun Pyo Kim Jun Pyo Kim Yu Hyun Park Mansu Kim Sang Won Seo Sang Won Seo Sang Won Seo |
| author_facet | Bo-Hyun Kim HyunWoo Lee Hongki Ham Hongki Ham Hee Jin Kim Hee Jin Kim Hee Jin Kim Hyemin Jang Hyemin Jang Hyemin Jang Hyemin Jang Jun Pyo Kim Jun Pyo Kim Jun Pyo Kim Yu Hyun Park Mansu Kim Sang Won Seo Sang Won Seo Sang Won Seo |
| author_sort | Bo-Hyun Kim |
| collection | DOAJ |
| description | Amyloid-beta (Aβ) is a pathological hallmark of Alzheimer’s disease (AD). We aimed to identify genes related to Aβ uptake in the Korean population and investigate the effects of these novel genes on clinical outcomes, including neurodegeneration and cognitive impairments. We recruited a total of 759 Korean participants who underwent neuropsychological tests, brain magnetic resonance imaging, 18F-flutemetamol positron emission tomography, and microarray genotyping data. We performed gene-based association analysis, and also performed expression quantitative trait loci and network analysis. In genome-wide association studies, no single nucleotide polymorphism (SNP) passed the genome-wide significance threshold. In gene-based association analysis, six genes (LCMT1, SCRN2, LRRC46, MRPL10, SP6, and OSBPL7) were significantly associated with Aβ standardised uptake value ratio in the brain. The three most significant SNPs (rs4787307, rs9903904, and rs11079797) on these genes are associated with the regulation of the LCMT1, OSBPL7, and SCRN2 genes, respectively. These SNPs are involved in decreasing hippocampal volume and cognitive scores by mediating Aβ uptake. The 19 enriched gene sets identified by pathway analysis included axon and chemokine activity. Our findings suggest novel susceptibility genes associated with the uptake of Aβ, which in turn leads to worse clinical outcomes. Our findings might lead to the discovery of new AD treatment targets. |
| first_indexed | 2024-03-11T18:37:55Z |
| format | Article |
| id | doaj.art-7de9efca8a7d4e4c8bd470afc17647cd |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-03-11T18:37:55Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-7de9efca8a7d4e4c8bd470afc17647cd2023-10-12T16:32:27ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-10-011510.3389/fnagi.2023.12789981278998Clinical effects of novel susceptibility genes for beta-amyloid: a gene-based association study in the Korean populationBo-Hyun Kim0HyunWoo Lee1Hongki Ham2Hongki Ham3Hee Jin Kim4Hee Jin Kim5Hee Jin Kim6Hyemin Jang7Hyemin Jang8Hyemin Jang9Hyemin Jang10Jun Pyo Kim11Jun Pyo Kim12Jun Pyo Kim13Yu Hyun Park14Mansu Kim15Sang Won Seo16Sang Won Seo17Sang Won Seo18Alzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of KoreaAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaNeuroscience Center, Samsung Medical Center, Seoul, Republic of KoreaAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaNeuroscience Center, Samsung Medical Center, Seoul, Republic of KoreaDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaNeuroscience Center, Samsung Medical Center, Seoul, Republic of KoreaDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Neurology, Seoul National University Hospital, Seoul, Republic of KoreaAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaNeuroscience Center, Samsung Medical Center, Seoul, Republic of KoreaDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaArtificial Intelligence Graduate School, Gwangju Institute of Science and Technology, Gwangju, Republic of KoreaAlzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaNeuroscience Center, Samsung Medical Center, Seoul, Republic of KoreaDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaAmyloid-beta (Aβ) is a pathological hallmark of Alzheimer’s disease (AD). We aimed to identify genes related to Aβ uptake in the Korean population and investigate the effects of these novel genes on clinical outcomes, including neurodegeneration and cognitive impairments. We recruited a total of 759 Korean participants who underwent neuropsychological tests, brain magnetic resonance imaging, 18F-flutemetamol positron emission tomography, and microarray genotyping data. We performed gene-based association analysis, and also performed expression quantitative trait loci and network analysis. In genome-wide association studies, no single nucleotide polymorphism (SNP) passed the genome-wide significance threshold. In gene-based association analysis, six genes (LCMT1, SCRN2, LRRC46, MRPL10, SP6, and OSBPL7) were significantly associated with Aβ standardised uptake value ratio in the brain. The three most significant SNPs (rs4787307, rs9903904, and rs11079797) on these genes are associated with the regulation of the LCMT1, OSBPL7, and SCRN2 genes, respectively. These SNPs are involved in decreasing hippocampal volume and cognitive scores by mediating Aβ uptake. The 19 enriched gene sets identified by pathway analysis included axon and chemokine activity. Our findings suggest novel susceptibility genes associated with the uptake of Aβ, which in turn leads to worse clinical outcomes. Our findings might lead to the discovery of new AD treatment targets.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1278998/fullAlzheimer’s diseasePETGWASamyloid-beta (Abeta)gene |
| spellingShingle | Bo-Hyun Kim HyunWoo Lee Hongki Ham Hongki Ham Hee Jin Kim Hee Jin Kim Hee Jin Kim Hyemin Jang Hyemin Jang Hyemin Jang Hyemin Jang Jun Pyo Kim Jun Pyo Kim Jun Pyo Kim Yu Hyun Park Mansu Kim Sang Won Seo Sang Won Seo Sang Won Seo Clinical effects of novel susceptibility genes for beta-amyloid: a gene-based association study in the Korean population Frontiers in Aging Neuroscience Alzheimer’s disease PET GWAS amyloid-beta (Abeta) gene |
| title | Clinical effects of novel susceptibility genes for beta-amyloid: a gene-based association study in the Korean population |
| title_full | Clinical effects of novel susceptibility genes for beta-amyloid: a gene-based association study in the Korean population |
| title_fullStr | Clinical effects of novel susceptibility genes for beta-amyloid: a gene-based association study in the Korean population |
| title_full_unstemmed | Clinical effects of novel susceptibility genes for beta-amyloid: a gene-based association study in the Korean population |
| title_short | Clinical effects of novel susceptibility genes for beta-amyloid: a gene-based association study in the Korean population |
| title_sort | clinical effects of novel susceptibility genes for beta amyloid a gene based association study in the korean population |
| topic | Alzheimer’s disease PET GWAS amyloid-beta (Abeta) gene |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1278998/full |
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