Identifying genetic variants for amyloid β in subcortical vascular cognitive impairment
BackgroundThe genetic basis of amyloid β (Aβ) deposition in subcortical vascular cognitive impairment (SVCI) is still unknown. Here, we investigated genetic variants involved in Aβ deposition in patients with SVCI.MethodsWe recruited a total of 110 patients with SVCI and 424 patients with Alzheimer’...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-04-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1160536/full |
| _version_ | 1797845037529169920 |
|---|---|
| author | Hang-Rai Kim Hang-Rai Kim Hang-Rai Kim Sang-Hyuk Jung Sang-Hyuk Jung Beomsu Kim Jaeho Kim Hyemin Jang Hyemin Jang Hyemin Jang Jun Pyo Kim Jun Pyo Kim So Yeon Kim So Yeon Kim So Yeon Kim So Yeon Kim Duk L. Na Duk L. Na Duk L. Na Hee Jin Kim Hee Jin Kim Hee Jin Kim Hee Jin Kim Kwangsik Nho Hong-Hee Won Hong-Hee Won Hong-Hee Won Sang Won Seo Sang Won Seo Sang Won Seo Sang Won Seo |
| author_facet | Hang-Rai Kim Hang-Rai Kim Hang-Rai Kim Sang-Hyuk Jung Sang-Hyuk Jung Beomsu Kim Jaeho Kim Hyemin Jang Hyemin Jang Hyemin Jang Jun Pyo Kim Jun Pyo Kim So Yeon Kim So Yeon Kim So Yeon Kim So Yeon Kim Duk L. Na Duk L. Na Duk L. Na Hee Jin Kim Hee Jin Kim Hee Jin Kim Hee Jin Kim Kwangsik Nho Hong-Hee Won Hong-Hee Won Hong-Hee Won Sang Won Seo Sang Won Seo Sang Won Seo Sang Won Seo |
| author_sort | Hang-Rai Kim |
| collection | DOAJ |
| description | BackgroundThe genetic basis of amyloid β (Aβ) deposition in subcortical vascular cognitive impairment (SVCI) is still unknown. Here, we investigated genetic variants involved in Aβ deposition in patients with SVCI.MethodsWe recruited a total of 110 patients with SVCI and 424 patients with Alzheimer’s disease-related cognitive impairment (ADCI), who underwent Aβ positron emission tomography and genetic testing. Using candidate AD-associated single nucleotide polymorphisms (SNPs) that were previously identified, we investigated Aβ-associated SNPs that were shared or distinct between patients with SVCI and those with ADCI. Replication analyses were performed using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and Rush Memory and Aging Project cohorts (ROS/MAP).ResultsWe identified a novel SNP, rs4732728, which showed distinct associations with Aβ positivity in patients with SVCI (Pinteraction = 1.49 × 10–5); rs4732728 was associated with increased Aβ positivity in SVCI but decreased Aβ positivity in ADCI. This pattern was also observed in ADNI and ROS/MAP cohorts. Prediction performance for Aβ positivity in patients with SVCI increased (area under the receiver operating characteristic curve = 0.780; 95% confidence interval = 0.757–0.803) when rs4732728 was included. Cis-expression quantitative trait loci analysis demonstrated that rs4732728 was associated with EPHX2 expression in the brain (normalized effect size = −0.182, P = 0.005).ConclusionThe novel genetic variants associated with EPHX2 showed a distinct effect on Aβ deposition between SVCI and ADCI. This finding may provide a potential pre-screening marker for Aβ positivity and a candidate therapeutic target for SVCI. |
| first_indexed | 2024-04-09T17:32:04Z |
| format | Article |
| id | doaj.art-ffe4d44d343043a99439cceb84ac286d |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-09T17:32:04Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-ffe4d44d343043a99439cceb84ac286d2023-04-18T05:03:25ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-04-011510.3389/fnagi.2023.11605361160536Identifying genetic variants for amyloid β in subcortical vascular cognitive impairmentHang-Rai Kim0Hang-Rai Kim1Hang-Rai Kim2Sang-Hyuk Jung3Sang-Hyuk Jung4Beomsu Kim5Jaeho Kim6Hyemin Jang7Hyemin Jang8Hyemin Jang9Jun Pyo Kim10Jun Pyo Kim11So Yeon Kim12So Yeon Kim13So Yeon Kim14So Yeon Kim15Duk L. Na16Duk L. Na17Duk L. Na18Hee Jin Kim19Hee Jin Kim20Hee Jin Kim21Hee Jin Kim22Kwangsik Nho23Hong-Hee Won24Hong-Hee Won25Hong-Hee Won26Sang Won Seo27Sang Won Seo28Sang Won Seo29Sang Won Seo30Department of Neurology, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, 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 KoreaDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of KoreaDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of KoreaDepartment of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, 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 KoreaDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of KoreaDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaDepartment of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of KoreaSamsung Genome Institute, Samsung Medical Center, Seoul, Republic of KoreaDepartment of Artificial Intelligence, Ajou University, Suwon, Republic of Korea0Department of Software and Computer Engineering, Ajou University, Suwon, 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 Korea1Cell and Gene Therapy Institute, Research Institute for Future Medicine, 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 KoreaDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea2Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of KoreaDepartment of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of KoreaSamsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea2Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, 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 Korea2Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea3Department of Intelligent Precision Healthcare Convergence, Seoul, Republic of KoreaBackgroundThe genetic basis of amyloid β (Aβ) deposition in subcortical vascular cognitive impairment (SVCI) is still unknown. Here, we investigated genetic variants involved in Aβ deposition in patients with SVCI.MethodsWe recruited a total of 110 patients with SVCI and 424 patients with Alzheimer’s disease-related cognitive impairment (ADCI), who underwent Aβ positron emission tomography and genetic testing. Using candidate AD-associated single nucleotide polymorphisms (SNPs) that were previously identified, we investigated Aβ-associated SNPs that were shared or distinct between patients with SVCI and those with ADCI. Replication analyses were performed using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and Rush Memory and Aging Project cohorts (ROS/MAP).ResultsWe identified a novel SNP, rs4732728, which showed distinct associations with Aβ positivity in patients with SVCI (Pinteraction = 1.49 × 10–5); rs4732728 was associated with increased Aβ positivity in SVCI but decreased Aβ positivity in ADCI. This pattern was also observed in ADNI and ROS/MAP cohorts. Prediction performance for Aβ positivity in patients with SVCI increased (area under the receiver operating characteristic curve = 0.780; 95% confidence interval = 0.757–0.803) when rs4732728 was included. Cis-expression quantitative trait loci analysis demonstrated that rs4732728 was associated with EPHX2 expression in the brain (normalized effect size = −0.182, P = 0.005).ConclusionThe novel genetic variants associated with EPHX2 showed a distinct effect on Aβ deposition between SVCI and ADCI. This finding may provide a potential pre-screening marker for Aβ positivity and a candidate therapeutic target for SVCI.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1160536/fullAlzheimer’s diseaseamyloid betapositron emission tomographysubcortical vascular cognitive impairment (SVCI)single nucleotide polymorphism (SNP) |
| spellingShingle | Hang-Rai Kim Hang-Rai Kim Hang-Rai Kim Sang-Hyuk Jung Sang-Hyuk Jung Beomsu Kim Jaeho Kim Hyemin Jang Hyemin Jang Hyemin Jang Jun Pyo Kim Jun Pyo Kim So Yeon Kim So Yeon Kim So Yeon Kim So Yeon Kim Duk L. Na Duk L. Na Duk L. Na Hee Jin Kim Hee Jin Kim Hee Jin Kim Hee Jin Kim Kwangsik Nho Hong-Hee Won Hong-Hee Won Hong-Hee Won Sang Won Seo Sang Won Seo Sang Won Seo Sang Won Seo Identifying genetic variants for amyloid β in subcortical vascular cognitive impairment Frontiers in Aging Neuroscience Alzheimer’s disease amyloid beta positron emission tomography subcortical vascular cognitive impairment (SVCI) single nucleotide polymorphism (SNP) |
| title | Identifying genetic variants for amyloid β in subcortical vascular cognitive impairment |
| title_full | Identifying genetic variants for amyloid β in subcortical vascular cognitive impairment |
| title_fullStr | Identifying genetic variants for amyloid β in subcortical vascular cognitive impairment |
| title_full_unstemmed | Identifying genetic variants for amyloid β in subcortical vascular cognitive impairment |
| title_short | Identifying genetic variants for amyloid β in subcortical vascular cognitive impairment |
| title_sort | identifying genetic variants for amyloid β in subcortical vascular cognitive impairment |
| topic | Alzheimer’s disease amyloid beta positron emission tomography subcortical vascular cognitive impairment (SVCI) single nucleotide polymorphism (SNP) |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1160536/full |
| work_keys_str_mv | AT hangraikim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT hangraikim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT hangraikim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT sanghyukjung identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT sanghyukjung identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT beomsukim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT jaehokim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT hyeminjang identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT hyeminjang identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT hyeminjang identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT junpyokim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT junpyokim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT soyeonkim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT soyeonkim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT soyeonkim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT soyeonkim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT duklna identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT duklna identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT duklna identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT heejinkim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT heejinkim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT heejinkim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT heejinkim identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT kwangsiknho identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT hongheewon identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT hongheewon identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT hongheewon identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT sangwonseo identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT sangwonseo identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT sangwonseo identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment AT sangwonseo identifyinggeneticvariantsforamyloidbinsubcorticalvascularcognitiveimpairment |