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dc.contributor.authorTan, Meng-Shan
dc.contributor.authorYang, Yu-Xiang
dc.contributor.authorXu, Wei
dc.contributor.authorWang, Hui-Fu
dc.contributor.authorTan, Lin
dc.contributor.authorZuo, Chuan-Tao
dc.contributor.authorDong, Qiang
dc.contributor.authorTan, Lan
dc.contributor.authorSuckling, John
dc.contributor.authorYu, Jin-Tai
dc.contributor.authorAlzheimer’s Disease Neuroimaging Initiative
dc.date.accessioned2021-03-13T00:31:13Z
dc.date.available2021-03-13T00:31:13Z
dc.date.issued2021-01-08
dc.identifier.issn1758-9193
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/318751
dc.description.abstractBACKGROUND: Genome-wide association studies have identified more than 30 Alzheimer's disease (AD) risk genes, although the detailed mechanism through which all these genes are associated with AD pathogenesis remains unknown. We comprehensively evaluate the roles of the variants in top 30 non-APOE AD risk genes, based on whether these variants were associated with altered mRNA transcript levels, as well as brain amyloidosis, tauopathy, and neurodegeneration. METHODS: Human brain gene expression data were obtained from the UK Brain Expression Consortium (UKBEC), while other data used in our study were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We examined the association of AD risk allele carrier status with the levels of gene expression in blood and brain regions and tested the association with brain amyloidosis, tauopathy, and neurodegeneration at baseline, using a multivariable linear regression model. Next, we analyzed the longitudinal effects of these variants on the change rates of pathology using a mixed effect model. RESULTS: Altogether, 27 variants were detected to be associated with the altered expression of 21 nearby genes in blood and brain regions. Eleven variants (especially novel variants in ADAM10, IGHV1-68, and SLC24A4/RIN3) were associated with brain amyloidosis, 7 variants (especially in INPP5D, PTK2B) with brain tauopathy, and 8 variants (especially in ECHDC3, HS3ST1) with brain neurodegeneration. Variants in ADAMTS1, BZRAP1-AS1, CELF1, CD2AP, and SLC24A4/RIN3 participated in more than one cerebral pathological process. CONCLUSIONS: Genetic variants might play functional roles and suggest potential mechanisms in AD pathogenesis, which opens doors to uncover novel targets for AD treatment.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAlzheimer’s Disease Neuroimaging Initiative
dc.subjectHumans
dc.subjectAlzheimer Disease
dc.subjectTauopathies
dc.subjectAmyloidosis
dc.subjectGene Expression
dc.subjectGenome-Wide Association Study
dc.titleAssociations of Alzheimer's disease risk variants with gene expression, amyloidosis, tauopathy, and neurodegeneration.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2021
prism.publicationNameAlzheimers Res Ther
prism.startingPage15
prism.volume13
dc.identifier.doi10.17863/CAM.65869
dcterms.dateAccepted2020-12-21
rioxxterms.versionofrecord10.1186/s13195-020-00755-7
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-01-08
dc.contributor.orcidYu, Jin-Tai [0000-0002-7686-0547]
dc.identifier.eissn1758-9193
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-01-08


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International