TitleGenome-wide association study identifies locus influencing human plasma tau levels.
Publication TypeJournal Article
Year of Publication2017
AuthorsChen J, Yu J-T, Wojta K, Wang H-F, Zetterberg H, Blennow K, Yokoyama JS, Weiner MW, Kramer JH, Rosen H, Miller BL, Coppola G, Boxer AL
Corporate AuthorsAlzheimer's Disease Neuroimaging Initiative
Date Published2017 Feb 14
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Apolipoprotein E4, Biomarkers, Cognitive Dysfunction, Cohort Studies, Endophenotypes, European Continental Ancestry Group, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Interleukin-2 Receptor alpha Subunit, Male, Middle Aged, Polymorphism, Single Nucleotide, tau Proteins, Ubiquitin-Protein Ligases, United States

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 () was associated with higher plasma tau levels at genome-wide significance ( = 4.85 × 10, empiric family-wise error corrected = 0.0024) in a dose-dependent fashion. This association was also observed in the replication cohort ( = 1.0 × 10; joint analysis = 1.2 × 10). Single nucleotide polymorphisms near (rs2187213) ( = 6.15 × 10), (rs7072793, rs7073236) ( = 7.89 × 10), and an intergenic locus on 9p21.3 (rs7047280) ( = 8.13 × 10) were identified as suggestive loci associated with plasma tau levels.

CONCLUSIONS: 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.

Alternate JournalNeurology
PubMed ID28100725
PubMed Central IDPMC5317386
Grant ListK01 AG049152 / AG / NIA NIH HHS / United States
K24 AG045333 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
U01 AG024904 / AG / NIA NIH HHS / United States
R01 AG038791 / AG / NIA NIH HHS / United States
U19 AG024904 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States
F31 NS084556 / NS / NINDS NIH HHS / United States
U54 NS092089 / NS / NINDS NIH HHS / United States