TY - JOUR
T1 - Evidence that common variation in NEDD9 is associated with susceptibility to late-onset Alzheimer's and Parkinson's disease
AU - Li, Yonghong
AU - Grupe, Andrew
AU - Rowland, Charles
AU - Holmans, Peter
AU - Segurado, Ricardo
AU - Abraham, Richard
AU - Jones, Lesley
AU - Catanese, Joseph
AU - Ross, David
AU - Mayo, Kevin
AU - Martinez, Maribel
AU - Hollingworth, Paul
AU - Goate, Alison
AU - Cairns, Nigel J.
AU - Racette, Brad A.
AU - Perlmutter, Joel S.
AU - O'Donovan, Michael C.
AU - Morris, John C.
AU - Brayne, Carol
AU - Rubinsztein, David C.
AU - Lovestone, Simon
AU - Thal, Leon J.
AU - Owen, Michael J.
AU - Williams, Julie
N1 - Funding Information:
Conflict of Interest statement. Y.L., A.G., C.R., D.R. and J.C. are employed by Celera. A.G. received research funding from and was a consultant to Celera. M.J.O. and J.W. received research funding from Celera.
PY - 2008/3/1
Y1 - 2008/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=39749165788&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddm348
DO - 10.1093/hmg/ddm348
M3 - Article
C2 - 18063669
AN - SCOPUS:39749165788
SN - 0964-6906
VL - 17
SP - 759
EP - 767
JO - Human molecular genetics
JF - Human molecular genetics
IS - 5
ER -