Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau), and Ab42 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 3 109 for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (p = 1.07 3 108 and p = 3.22 3 109 for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p = 3.58 3 108 for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recentlyreported 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 3 104, 0.039, 4.86 3 105, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci.