@article{c036a67910d445e7aee08ad92f0495ce,
title = "GWAS of cerebrospinal fluid tau levels identifies risk variants for alzheimer's disease",
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",
author = "Carlos Cruchaga and Kauwe, {John S.K.} and Oscar Harari and Jin, {Sheng Chih} and Yefei Cai and Karch, {Celeste M.} and Benitez, {Bruno A.} and Jeng, {Amanda T.} and Tara Skorupa and David Carrell and Sarah Bertelsen and Matthew Bailey and David McKean and Shulman, {Joshua M.} and {De Jager}, {Philip L.} and Lori Chibnik and Bennett, {David A.} and Arnold, {Steve E.} and Denise Harold and Rebecca Sims and Amy Gerrish and Julie Williams and {Van Deerlin}, {Vivianna M.} and Lee, {Virginia M.Y.} and Shaw, {Leslie M.} and Trojanowski, {John Q.} and Haines, {Jonathan L.} and Richard Mayeux and Pericak-Vance, {Margaret A.} and Farrer, {Lindsay A.} and Schellenberg, {Gerard D.} and Peskind, {Elaine R.} and Douglas Galasko and Fagan, {Anne M.} and Holtzman, {David M.} and Morris, {John C.} and Goate, {Alison M.}",
note = "Funding Information: This work was supported by grants from NIH (P30 NS069329-01, R01 AG035083, R01 AG16208, P50 AG05681, P01 AG03991, P01 AG026276, AG05136 and PO1 AG05131, U01AG032984, AG010124, and R01 AG042611), AstraZeneca, and the Barnes-Jewish Hospital Foundation. The authors thank the Clinical and Genetics Cores of the Knight ADRC at Washington University for clinical and cognitive assessments of the participants and for APOE genotypes and the Biomarker Core of the Adult Children Study at Washington University for the CSF collection and assays. We acknowledge use of genotype data from the “610 group,” part of the GERAD1 consortium, who were supported by funding from the Wellcome Trust (including GR082604MA), Medical Research Council (including G0300429), Alzheimer{\textquoteright}s Research Trust, Welsh Assembly Government, Alzheimer{\textquoteright}s Society, Ulster Garden Villages, Northern Ireland R&D Office, Royal College of Physicians/Dunhill Medical Trust, Mercer{\textquoteright}s Institute for Research on Ageing, Bristol Research into Alzheimer{\textquoteright}s and Care of the Elderly (BRACE), Charles Wolfson Charitable Trust, NIH (including PO1 AG026276, PO1 AG03991, RO1 AG16208, and P50 AG05681), NIA, Barnes Jewish Hospital Foundation, Charles and Joanne Knight Alzheimer{\textquoteright}s Research Initiative of the Washington University Alzheimer{\textquoteright}s Disease Research Centre, the UCLH/UCL Biomedical Centre, Lundbeck SA, German Federal Ministry of Education and Research (BMBF): Kompetenznetz Demenzen (01GI0420), Bundesministerium f{\"u}r Bildung und Forschung, and Competence Network Dementia (CND) F{\"o}rderkennzeichen (01GI0102, 01GI0711). Recruitment and CSF studies at University of Washington and UCSD were supported by NIH PO1 AGO5131. Replication analysis in the Religious Orders Study and Rush Memory and Aging Project cohorts was supported by grants from the National Institutes of Health (R01 AG30146, P30 AG10161, R01 AG17917, R01 AG15819, and K08 AG034290), the Illinois Department of Public Health, and the Burroughs Wellcome Fund. Data collection and sharing for this project were funded by the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). D.M.H. is a cofounder of C2N Diagnostics and serves of the C2N Scientific Advisory Board. He also consults for Genentech, AstraZeneca, and Bristol Myers Squibb. His laboratory also receives research grants from Pfizer, Eli Lilly, AstraZeneca, and C2N Diagnostics. ",
year = "2013",
month = apr,
day = "24",
doi = "10.1016/j.neuron.2013.02.026",
language = "English (US)",
volume = "78",
pages = "256--268",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",
}