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dc.contributor.authorTan, Meng-Shanen
dc.contributor.authorYang, Yu-Xiangen
dc.contributor.authorXu, Weien
dc.contributor.authorWang, Hui-Fuen
dc.contributor.authorTan, Linen
dc.contributor.authorZuo, Chuan-Taoen
dc.contributor.authorDong, Qiangen
dc.contributor.authorTan, Lanen
dc.contributor.authorSuckling, Johnen
dc.contributor.authorYu, Jin-Taien
dc.date.accessioned2021-01-08T17:22:16Z
dc.date.available2021-01-08T17:22:16Z
dc.date.issued2021-01-08
dc.date.submitted2020-06-25
dc.identifier.others13195-020-00755-7
dc.identifier.other755
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/315932
dc.descriptionFunder: ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University
dc.description.abstractAbstract: Background: 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.languageen
dc.publisherBioMed Central
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch
dc.subjectAlzheimer disease
dc.subjectAmyloid
dc.subjectTau
dc.subjectNeurodegeneration
dc.subjectRisk variants
dc.subjectGene expression
dc.titleAssociations of Alzheimer’s disease risk variants with gene expression, amyloidosis, tauopathy, and neurodegeneration
dc.typeArticle
dc.date.updated2021-01-08T17:22:16Z
prism.issueIdentifier1
prism.publicationNameAlzheimer's Research & Therapy
prism.volume13
dc.identifier.doi10.17863/CAM.63043
dcterms.dateAccepted2020-12-21
rioxxterms.versionofrecord10.1186/s13195-020-00755-7
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidYu, Jin-Tai [0000-0002-7686-0547]
dc.identifier.eissn1758-9193
pubs.funder-project-idNational Natural Science Foundation of China (91849126)
pubs.funder-project-idNational Key R&D Program of China (2018YFC1314700)
pubs.funder-project-idTaishan Scholar Project of Shandong Province (tsqn20161078)
pubs.funder-project-idShanghai Municipal Science and Technology Major Project (No.2018SHZDZX01)


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