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.
journal_name
Neuronjournal_title
Neuronauthors
Cruchaga C,Kauwe JS,Harari O,Jin SC,Cai Y,Karch CM,Benitez BA,Jeng AT,Skorupa T,Carrell D,Bertelsen S,Bailey M,McKean D,Shulman JM,De Jager PL,Chibnik L,Bennett DA,Arnold SE,Harold D,Sims R,Gerrish A,Williams Jdoi
10.1016/j.neuron.2013.02.026subject
Has Abstractpub_date
2013-04-24 00:00:00pages
256-68issue
2eissn
0896-6273issn
1097-4199pii
S0896-6273(13)00184-0journal_volume
78pub_type
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