文摘
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Summary
Cerebrospinal fluid (CSF) tau, tau phosphorylated at?threonine 181 (ptau), and A¦Â42 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?¡Á 10?9 for tau) located at 3q28?between GEMC1 and OSTN, rs514716 (p?= 1.07?¡Á 10?8 and p?= 3.22?¡Á 10?9 for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p?= 3.58?¡Á 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?¡Á 10?4, 0.039, 4.86?¡Á 10?5, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci.
