GWAS of cerebrospinal fluid tau levels identifies risk variants for alzheimer's disease

Carlos Cruchaga, 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 SimsAmy 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

Research output: Contribution to journalArticlepeer-review

261 Scopus citations


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

Original languageEnglish
Pages (from-to)256-268
Number of pages13
Issue number2
StatePublished - Apr 24 2013


Dive into the research topics of 'GWAS of cerebrospinal fluid tau levels identifies risk variants for alzheimer's disease'. Together they form a unique fingerprint.

Cite this