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Genome-wide association study identifies MAPT locus influencing human plasma tau levels.
Chen, Jason; Yu, Jin-Tai; Wojta, Kevin; Wang, Hui-Fu; Zetterberg, Henrik; Blennow, Kaj; Yokoyama, Jennifer S; Weiner, Michael W; Kramer, Joel H; Rosen, Howard; Miller, Bruce L; Coppola, Giovanni; Boxer, Adam L.
Afiliação
  • Chen J; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Yu JT; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Wojta K; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Wang HF; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Zetterberg H; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Blennow K; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Yokoyama JS; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Weiner MW; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Kramer JH; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Rosen H; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Miller BL; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Coppola G; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
  • Boxer AL; From the Department of Neurology (J.C., K.W., G.C.), David Geffen School of Medicine, and Memory and Aging Center (J.S.Y., J.H.K., H.R., B.L.M., A.L.B.), Department of Neurology, University of California, Los Angeles; Department of Neurology (J.-T.Y., H.-F.W.), Qingdao Municipal Hospital, Nanjing Me
Neurology ; 88(7): 669-676, 2017 Feb 14.
Article em En | MEDLINE | ID: mdl-28100725
OBJECTIVE: To identify genetic loci associated with plasma tau concentrations in healthy elders and individuals with Alzheimer disease. METHODS: Four hundred sixty-three non-Hispanic white individuals exceeding quality control criteria were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1) cohort. Association of plasma tau with genetic polymorphisms was performed with a linear regression model. Significant associations were validated in an independent replication cohort consisting of 431 healthy elders or individuals with mild cognitive impairment recruited from the University of California, San Francisco Memory and Aging Center. RESULTS: The minor allele (A) of rs242557 in the microtubule-associated protein tau gene (MAPT) was associated with higher plasma tau levels at genome-wide significance (p = 4.85 × 10-9, empiric family-wise error corrected p = 0.0024) in a dose-dependent fashion. This association was also observed in the replication cohort (p = 1.0 × 10-5; joint analysis p = 1.2 × 10-12). Single nucleotide polymorphisms near PARK2 (rs2187213) (p = 6.15 × 10-6), IL2RA (rs7072793, rs7073236) (p = 7.89 × 10-6), and an intergenic locus on 9p21.3 (rs7047280) (p = 8.13 × 10-6) were identified as suggestive loci associated with plasma tau levels. CONCLUSIONS: MAPT H1c haplotype (rs242557) has previously been identified as a genetic risk factor for progressive supranuclear palsy and corticobasal degeneration. The current findings suggest that plasma tau concentration could be an endophenotype for identifying risk for 4-repeat tauopathies in older individuals.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas tau / Doença de Alzheimer / Disfunção Cognitiva Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged País/Região como assunto: America do norte Idioma: En Revista: Neurology Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas tau / Doença de Alzheimer / Disfunção Cognitiva Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged País/Região como assunto: America do norte Idioma: En Revista: Neurology Ano de publicação: 2017 Tipo de documento: Article