GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer's Disease

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2013 Apr 9

PMID 23562540

Citations 236

Authors

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 Sims

Amy 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

Affiliations

Soon will be listed here.

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.

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