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dc.contributor.authorTang, Min
dc.contributor.authorAlaniz, Maria Eugenia
dc.contributor.authorFelsky, Daniel
dc.contributor.authorVardarajan, Badri
dc.contributor.authorReyes-Dumeyer, Dolly
dc.contributor.authorLantigua, Rafael
dc.contributor.authorMedrano, Martin
dc.contributor.authorBennett, David A
dc.contributor.authorDe Jager, Philip L
dc.contributor.authorMayeux, Richard
dc.contributor.authorSanta-Maria, Ismael
dc.contributor.authorReitz, Christiane
dc.date.accessioned2021-04-23T19:34:12Z
dc.date.available2021-04-23T19:34:12Z
dc.date.issued2020-06-08
dc.identifier.citationTang, M., Alaniz, M. E., Felsky, D., Vardarajan, B., Reyes-Dumeyer, D., Lantigua, R., ... & Reitz, C. (2020). Synonymous variants associated with Alzheimer disease in multiplex families. Neurology Genetics, 6(4).en_US
dc.identifier.issn2376-7839
dc.identifier.pmid32637632
dc.identifier.doi10.1212/NXG.0000000000000450
dc.identifier.urihttp://hdl.handle.net/10150/657905
dc.description.abstractRare synonymous variants in 4 genes (CDH23, SLC9A3R1, RHBDD2, and ITIH2) segregated with AD status in multiplex families and had a significantly higher frequency in these families compared with reference populations of similar ancestry. In comparison to subjects without dementia, expression of CDH23 (β = 0.53, p = 0.006) and SLC9A3R1 (β = 0.50, p = 0.02) was increased, and expression of RHBDD2 (β = -0.70, p = 0.02) decreased in individuals with AD at death. In line with this finding, increased expression of CDH23 (β = 0.26 ± 0.08, p = 4.9E-4) and decreased expression of RHBDD2 (β = -0.60 ± 0.12, p = 5.5E-7) were related to brain amyloid load (p = 0.0025). SLC9A3R1 expression was associated with burden of TDP43 pathology (β = 0.58 ± 0.17, p = 5.9E-4). Using eQTL data, the CDH23 variant was in linkage disequilibrium with variants modulating CDH23 expression levels (top single nucleotide polymorphism: rs11000035, p = 4.85E-6, D' = 1.0). Using minigene splicing assays, the CDH23 and SLC9A3R1 variants affected splicing efficiency.en_US
dc.language.isoenen_US
dc.publisherLIPPINCOTT WILLIAMS & WILKINSen_US
dc.rightsCopyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleSynonymous variants associated with Alzheimer disease in multiplex familiesen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Pharmacol, Ctr Innovat Brain Scien_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Neurol, Ctr Innovat Brain Scien_US
dc.identifier.journalNEUROLOGY-GENETICSen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleNeurology. Genetics
dc.source.volume6
dc.source.issue4
dc.source.beginpagee450
dc.source.endpage
refterms.dateFOA2021-04-23T19:34:13Z
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States


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Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Except where otherwise noted, this item's license is described as Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).