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dc.contributor.authorJakobsdottir, Johannaen_US
dc.contributor.authorvan der Lee, Sven J.en_US
dc.contributor.authorBis, Joshua C.en_US
dc.contributor.authorChouraki, Vincenten_US
dc.contributor.authorLi-Kroeger, Daviden_US
dc.contributor.authorYamamoto, Shinyaen_US
dc.contributor.authorGrove, Megan L.en_US
dc.contributor.authorNaj, Adamen_US
dc.contributor.authorVronskaya, Mariaen_US
dc.contributor.authorSalazar, Jose L.en_US
dc.contributor.authorDeStefano, Anita L.en_US
dc.contributor.authorBrody, Jennifer A.en_US
dc.contributor.authorSmith, Albert V.en_US
dc.contributor.authorAmin, Najafen_US
dc.contributor.authorSims, Rebeccaen_US
dc.contributor.authorIbrahim-Verbaas, Carla A.en_US
dc.contributor.authorChoi, Seung-Hoanen_US
dc.contributor.authorSatizabal, Claudia L.en_US
dc.contributor.authorLopez, Oscar L.en_US
dc.contributor.authorBeiser, Alexaen_US
dc.contributor.authorIkram, M. Arfanen_US
dc.contributor.authorGarcia, Melissa E.en_US
dc.contributor.authorHayward, Carolineen_US
dc.contributor.authorVarga, Tibor V.en_US
dc.contributor.authorRipatti, Samulien_US
dc.contributor.authorFranks, Paul W.en_US
dc.contributor.authorHallmans, Göranen_US
dc.contributor.authorRolandsson, Oloven_US
dc.contributor.authorJansson, Jan-Håkonen_US
dc.contributor.authorPorteous, David J.en_US
dc.contributor.authorSalomaa, Veikkoen_US
dc.contributor.authorEiriksdottir, Gudnyen_US
dc.contributor.authorRice, Kenneth M.en_US
dc.contributor.authorBellen, Hugo J.en_US
dc.contributor.authorLevy, Danielen_US
dc.contributor.authorUitterlinden, Andre G.en_US
dc.contributor.authorEmilsson, Valuren_US
dc.contributor.authorRotter, Jerome I.en_US
dc.contributor.authorAspelund, Thoren_US
dc.contributor.authorO’Donnell, Christopher J.en_US
dc.contributor.authorFitzpatrick, Annette L.en_US
dc.contributor.authorLauner, Lenore J.en_US
dc.contributor.authorHofman, Alberten_US
dc.contributor.authorWang, Li-Sanen_US
dc.contributor.authorWilliams, Julieen_US
dc.contributor.authorSchellenberg, Gerard D.en_US
dc.contributor.authorBoerwinkle, Ericen_US
dc.contributor.authorPsaty, Bruce M.en_US
dc.contributor.authorSeshadri, Sudhaen_US
dc.contributor.authorShulman, Joshua M.en_US
dc.contributor.authorGudnason, Vilmunduren_US
dc.contributor.authorvan Duijn, Cornelia M.en_US
dc.date.accessioned2016-11-18T20:47:44Z
dc.date.issued2016en_US
dc.identifier.citationJakobsdottir, J., S. J. van der Lee, J. C. Bis, V. Chouraki, D. Li-Kroeger, S. Yamamoto, M. L. Grove, et al. 2016. “Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease.” PLoS Genetics 12 (10): e1006327. doi:10.1371/journal.pgen.1006327. http://dx.doi.org/10.1371/journal.pgen.1006327.en
dc.identifier.issn1553-7390en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29408358
dc.description.abstractWe performed an exome-wide association analysis in 1393 late-onset Alzheimer’s disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (~0.5% versus <0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES sub-study, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5–15.9), p = 6.6x10-9]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the β-amyloid cascade.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pgen.1006327en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072721/pdf/en
dash.licenseLAAen_US
dc.subjectMedicine and Health Sciencesen
dc.subjectMental Health and Psychiatryen
dc.subjectDementiaen
dc.subjectAlzheimer Diseaseen
dc.subjectNeurologyen
dc.subjectNeurodegenerative Diseasesen
dc.subjectModel Organismsen
dc.subjectAnimal Modelsen
dc.subjectDrosophila Melanogasteren
dc.subjectBiology and Life Sciencesen
dc.subjectOrganismsen
dc.subjectAnimalsen
dc.subjectInvertebratesen
dc.subjectArthropodaen
dc.subjectInsectsen
dc.subjectDrosophilaen
dc.subjectDevelopmental Biologyen
dc.subjectEmbryologyen
dc.subjectEmbryosen
dc.subjectGeneticsen
dc.subjectGenetic Locien
dc.subjectAllelesen
dc.subjectPhenotypesen
dc.subjectGenomicsen
dc.subjectAnimal Genomicsen
dc.subjectInvertebrate Genomicsen
dc.subjectCell Biologyen
dc.subjectSignal Transductionen
dc.subjectCell Signalingen
dc.subjectNotch Signalingen
dc.subjectSocial Sciencesen
dc.subjectSociologyen
dc.subjectConsortiaen
dc.titleRare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Diseaseen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Geneticsen
dash.depositing.authorFranks, Paul W.en_US
dc.date.available2016-11-18T20:47:44Z
dc.identifier.doi10.1371/journal.pgen.1006327*
dash.authorsorderedfalse
dash.contributor.affiliatedFranks, Paul


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