Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer’s disease

IntroductionAlzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cerebral cortex atrophy. In this study, we used sparse canonical correlation analysis (SCCA) to identify associations between single nucleotide polymorphisms (SNPs) and cortical thickness in the Korean p...

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Main Authors: Bo-Hyun Kim, Sang Won Seo, Yu Hyun Park, JiHyun Kim, Hee Jin Kim, Hyemin Jang, Jihwan Yun, Mansu Kim, Jun Pyo Kim
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-09-01
Series:Frontiers in Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2024.1428900/full
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author Bo-Hyun Kim
Sang Won Seo
Sang Won Seo
Sang Won Seo
Yu Hyun Park
JiHyun Kim
Hee Jin Kim
Hee Jin Kim
Hee Jin Kim
Hyemin Jang
Hyemin Jang
Hyemin Jang
Hyemin Jang
Jihwan Yun
Jihwan Yun
Jihwan Yun
Jihwan Yun
Mansu Kim
Jun Pyo Kim
Jun Pyo Kim
Jun Pyo Kim
author_facet Bo-Hyun Kim
Sang Won Seo
Sang Won Seo
Sang Won Seo
Yu Hyun Park
JiHyun Kim
Hee Jin Kim
Hee Jin Kim
Hee Jin Kim
Hyemin Jang
Hyemin Jang
Hyemin Jang
Hyemin Jang
Jihwan Yun
Jihwan Yun
Jihwan Yun
Jihwan Yun
Mansu Kim
Jun Pyo Kim
Jun Pyo Kim
Jun Pyo Kim
author_sort Bo-Hyun Kim
collection DOAJ
description IntroductionAlzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cerebral cortex atrophy. In this study, we used sparse canonical correlation analysis (SCCA) to identify associations between single nucleotide polymorphisms (SNPs) and cortical thickness in the Korean population. We also investigated the role of the SNPs in neurological outcomes, including neurodegeneration and cognitive dysfunction.MethodsWe recruited 1125 Korean participants who underwent neuropsychological testing, brain magnetic resonance imaging, positron emission tomography, and microarray genotyping. We performed group-wise SCCA in Aβ negative (−) and Aβ positive (+) groups. In addition, we performed mediation, expression quantitative trait loci, and pathway analyses to determine the functional role of the SNPs.ResultsWe identified SNPs related to cortical thickness using SCCA in Aβ negative and positive groups and identified SNPs that improve the prediction performance of cognitive impairments. Among them, rs9270580 was associated with cortical thickness by mediating Aβ uptake, and three SNPs (rs2271920, rs6859, rs9270580) were associated with the regulation of CHRNA2, NECTIN2, and HLA genes.ConclusionOur findings suggest that SNPs potentially contribute to cortical thickness in AD, which in turn leads to worse clinical outcomes. Our findings contribute to the understanding of the genetic architecture underlying cortical atrophy and its relationship with AD.
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spelling doaj-art-68f6346a2e8c4ef28bbe9f75e695eac72025-08-20T01:54:26ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2024-09-011810.3389/fnins.2024.14289001428900Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer’s diseaseBo-Hyun Kim0Sang Won Seo1Sang Won Seo2Sang Won Seo3Yu Hyun Park4JiHyun Kim5Hee Jin Kim6Hee Jin Kim7Hee Jin Kim8Hyemin Jang9Hyemin Jang10Hyemin Jang11Hyemin Jang12Jihwan Yun13Jihwan Yun14Jihwan Yun15Jihwan Yun16Mansu Kim17Jun Pyo Kim18Jun Pyo Kim19Jun Pyo Kim20Alzheimer’s Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaAlzheimer’s Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaNeuroscience Center, Samsung Medical Center, Seoul, Republic of KoreaAlzheimer’s Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaAlzheimer’s Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaAlzheimer’s Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaNeuroscience Center, Samsung Medical Center, Seoul, Republic of KoreaAlzheimer’s Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of KoreaDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaNeuroscience Center, Samsung Medical Center, 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 KoreaDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaNeuroscience Center, Samsung Medical Center, Seoul, Republic of KoreaDepartment of Neurology, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, 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 KoreaDepartment of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaNeuroscience Center, Samsung Medical Center, Seoul, Republic of KoreaIntroductionAlzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cerebral cortex atrophy. In this study, we used sparse canonical correlation analysis (SCCA) to identify associations between single nucleotide polymorphisms (SNPs) and cortical thickness in the Korean population. We also investigated the role of the SNPs in neurological outcomes, including neurodegeneration and cognitive dysfunction.MethodsWe recruited 1125 Korean participants who underwent neuropsychological testing, brain magnetic resonance imaging, positron emission tomography, and microarray genotyping. We performed group-wise SCCA in Aβ negative (−) and Aβ positive (+) groups. In addition, we performed mediation, expression quantitative trait loci, and pathway analyses to determine the functional role of the SNPs.ResultsWe identified SNPs related to cortical thickness using SCCA in Aβ negative and positive groups and identified SNPs that improve the prediction performance of cognitive impairments. Among them, rs9270580 was associated with cortical thickness by mediating Aβ uptake, and three SNPs (rs2271920, rs6859, rs9270580) were associated with the regulation of CHRNA2, NECTIN2, and HLA genes.ConclusionOur findings suggest that SNPs potentially contribute to cortical thickness in AD, which in turn leads to worse clinical outcomes. Our findings contribute to the understanding of the genetic architecture underlying cortical atrophy and its relationship with AD.https://www.frontiersin.org/articles/10.3389/fnins.2024.1428900/fullAlzheimer’s diseasesparse canonical correlation analysisgeneticscortical thicknessamyloid beta (Ab)single nucleotide polymorphism (SNP)
spellingShingle Bo-Hyun Kim
Sang Won Seo
Sang Won Seo
Sang Won Seo
Yu Hyun Park
JiHyun Kim
Hee Jin Kim
Hee Jin Kim
Hee Jin Kim
Hyemin Jang
Hyemin Jang
Hyemin Jang
Hyemin Jang
Jihwan Yun
Jihwan Yun
Jihwan Yun
Jihwan Yun
Mansu Kim
Jun Pyo Kim
Jun Pyo Kim
Jun Pyo Kim
Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer’s disease
Frontiers in Neuroscience
Alzheimer’s disease
sparse canonical correlation analysis
genetics
cortical thickness
amyloid beta (Ab)
single nucleotide polymorphism (SNP)
title Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer’s disease
title_full Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer’s disease
title_fullStr Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer’s disease
title_full_unstemmed Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer’s disease
title_short Clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in Alzheimer’s disease
title_sort clinical application of sparse canonical correlation analysis to detect genetic associations with cortical thickness in alzheimer s disease
topic Alzheimer’s disease
sparse canonical correlation analysis
genetics
cortical thickness
amyloid beta (Ab)
single nucleotide polymorphism (SNP)
url https://www.frontiersin.org/articles/10.3389/fnins.2024.1428900/full
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