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Genome-wide associa...
Genome-wide association study identifies MAPT locus influencing human plasma tau levels
- Article/chapterEnglish2017
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2017-01-18
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Ovid Technologies (Wolters Kluwer Health),2017
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LIBRIS-ID:oai:gup.ub.gu.se/252456
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https://gup.ub.gu.se/publication/252456URI
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https://doi.org/10.1212/wnl.0000000000003615DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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 x 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 x 10(-5); joint analysis p = 1.2 x 10(-12)). Single nucleotide polymorphisms near PARK2 (rs2187213) (p = 6.15 x 10(-6)), IL2RA (rs7072793, rs7073236) (p = 7.89 x 10(-6)), and an intergenic locus on 9p21.3 (rs7047280) (p = 8.13 x 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.
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Yu, J. T.
(author)
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Wojta, K.
(author)
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Wang, H. F.
(author)
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Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe
(author)
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Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka
(author)
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Yokoyama, J. S.
(author)
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Weiner, M. W.
(author)
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Kramer, J. H.
(author)
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Rosen, H.
(author)
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Miller, B. L.
(author)
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Coppola, G.
(author)
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Boxer, A. L.
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
(creator_code:org_t)
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In:Neurology: Ovid Technologies (Wolters Kluwer Health)88:7, s. 669-6760028-38781526-632X
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Chen, J.
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Yu, J. T.
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Wojta, K.
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Wang, H. F.
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Zetterberg, Henr ...
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Blennow, Kaj, 19 ...
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Yokoyama, J. S.
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Weiner, M. W.
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Kramer, J. H.
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Rosen, H.
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Miller, B. L.
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Coppola, G.
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Boxer, A. L.
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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Neurology
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University of Gothenburg