Evidence that common variation in NEDD9 is associated with susceptibility to late-onset Alzheimer's and Parkinson's disease

Yonghong Li, Andrew Grupe, Charles Rowland, Peter Holmans, Ricardo Segurado, Richard Abraham, Lesley Jones, Joseph Catanese, David Ross, Kevin Mayo, Maribel Martinez, Paul Hollingworth, Alison Goate, Nigel J. Cairns, Brad A. Racette, Joel S. Perlmutter, Michael C. O'Donovan, John C. Morris, Carol Brayne, David C. RubinszteinSimon Lovestone, Leon J. Thal, Michael J. Owen, Julie Williams

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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 4692 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 = 3521, P = 5.38×10-6, 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 = 1464, 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.

Original languageEnglish
Pages (from-to)759-767
Number of pages9
JournalHuman molecular genetics
Volume17
Issue number5
DOIs
StatePublished - Mar 1 2008

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    Li, Y., Grupe, A., Rowland, C., Holmans, P., Segurado, R., Abraham, R., Jones, L., Catanese, J., Ross, D., Mayo, K., Martinez, M., Hollingworth, P., Goate, A., Cairns, N. J., Racette, B. A., Perlmutter, J. S., O'Donovan, M. C., Morris, J. C., Brayne, C., ... Williams, J. (2008). Evidence that common variation in NEDD9 is associated with susceptibility to late-onset Alzheimer's and Parkinson's disease. Human molecular genetics, 17(5), 759-767. https://doi.org/10.1093/hmg/ddm348