| Literature DB >> 23562540 |
Carlos Cruchaga1, John S K Kauwe, Oscar Harari, Sheng Chih Jin, Yefei Cai, Celeste M Karch, Bruno A Benitez, Amanda T Jeng, Tara Skorupa, David Carrell, Sarah Bertelsen, Matthew Bailey, David McKean, Joshua M Shulman, Philip L De Jager, Lori Chibnik, David A Bennett, Steve E Arnold, Denise Harold, Rebecca Sims, Amy Gerrish, Julie Williams, Vivianna M Van Deerlin, Virginia M-Y Lee, Leslie M Shaw, John Q Trojanowski, Jonathan L Haines, Richard Mayeux, Margaret A Pericak-Vance, Lindsay A Farrer, Gerard D Schellenberg, Elaine R Peskind, Douglas Galasko, Anne M Fagan, David M Holtzman, John C Morris, Alison M Goate.
Abstract
Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau), and Aβ₄₂ are established biomarkers for Alzheimer's disease (AD) and have been used as quantitative traits for genetic analyses. We performed the largest genome-wide association study for cerebrospinal fluid (CSF) tau/ptau levels published to date (n = 1,269), identifying three genome-wide significant loci for CSF tau and ptau: rs9877502 (p = 4.89 × 10⁻⁹ for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (p = 1.07 × 10⁻⁸ and p = 3.22 × 10⁻⁹ for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p = 3.58 × 10⁻⁸ for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk. In independent data sets, rs9877502 showed a strong association with risk for AD, tangle pathology, and global cognitive decline (p = 2.67 × 10⁻⁴, 0.039, 4.86 × 10⁻⁵, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci.Entities:
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Year: 2013 PMID： 23562540 PMCID： PMC3664945 DOI： 10.1016/j.neuron.2013.02.026
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173