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Human Molecular Genetics Advance Access published online on December 6, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm348
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Evidence that Common Variation in NEDD9 is Associated with Susceptibility to Late-onset Alzheimer's and Parkinson's Disease

Yonghong Li1, Andrew Grupe1,*, Charles Rowland1, Peter Holmans2, Ricardo Segurado2, Richard Abraham2, Lesley Jones2, Joseph Catanese1, David Ross1, Kevin Mayo3, Maribel Martinez3, Paul Hollingworth2, Carol Brayne4, David C Rubinsztein4, Nigel J. Cairns3, Brad A. Racette3, Joel S. Perlmutter3, Michael C. O'Donovan2, John C. Morris3, Simon Lovestone5, Leon J. Thal6,{dagger}, Michael J. Owen2, Alison Goate3 and Julie Williams2

1 Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA 2 Department of Psychological Medicine & Biostatistics and Bioinformatics Unit, Wales School of Medicine, Cardiff University, Cardiff CF14 4XN, UK 3 Departments of Psychiatry, Neurology, Genetics, Pathology & Immunology, Radiology, and Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA 4 Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrookés Hopsital, Cambridge CB2 2XY, UK 5 MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London, London SE5 8AF, UK 6 Department of Neurosciences, University of California, San Diego, La Jolla CA 92093, USA

* To whom correspondence should be addressed at Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502. Tel; +1 5107496222; Fax: +1 5107496286; E-mail: andrew.grupe{at}celera.com

Received September 21, 2007; Revised November 21, 2007; Accepted November 21, 2007

Late-onset Alzheimer's disease (LOAD) and Parkinson's disease (PD) are the most common neurodegenerative disorders and in both diseases susceptibility is known to be influenced by genes. We set out to identify novel susceptibility genes for LOAD by performing a large scale, multi-tiered association study testing 4,692 single nucleotide polymorphism (SNPs). We identified a SNP within a putative transcription factor binding site in the NEDD9 gene (neural precursor cell expressed, developmentally down-regulated), that shows good evidence of association with disease risk in four out of five LOAD samples (N= 3,521, P= 5.38x10–6, odds ratio (OR)= 1.38 [1.20 - 1.59]) and in addition, we observed a similar pattern of association in two PD sample sets ( N= 1,464, P= 0.0145, OR= 1.31 [1.05 – 1.62]). In exploring a potential mechanism for the association, we observed that expression of NEDD9 and APOE show a strong inverse correlation in the hippocampus of Alzheimer's cases. These data implicate NEDD9 as a novel susceptibility gene for LOAD and possibly PD.

{dagger} This paper is dedicated to the memory of Leon Thal for his many contributions to Alzheimer's research and patient therapy.


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J. Chapuis, F. Moisan, G. Mellick, A. Elbaz, P. Silburn, F. Pasquier, D. Hannequin, C. Lendon, D. Campion, P. Amouyel, et al.
Association study of the NEDD9 gene with the risk of developing Alzheimer's and Parkinson's disease
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