Evidence that common variation in NEDD9 is associated with susceptibility to late-onset Alzheimer's and Parkinson's disease.
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 = 5.38x10(-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 = 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.
Li
Yonghong
Y
Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA.
Grupe
Andrew
A
Rowland
Charles
C
Holmans
Peter
P
Segurado
Ricardo
R
Abraham
Richard
R
Jones
Lesley
L
Catanese
Joseph
J
Ross
David
D
Mayo
Kevin
K
Martinez
Maribel
M
Hollingworth
Paul
P
Goate
Alison
A
Cairns
Nigel J
NJ
Racette
Brad A
BA
Perlmutter
Joel S
JS
O'Donovan
Michael C
MC
Morris
John C
JC
Brayne
Carol
C
Rubinsztein
David C
DC
Lovestone
Simon
S
Thal
Leon J
LJ
Owen
Michael J
MJ
Williams
Julie
J
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D004198:Disease Susceptibility; D015870:Gene Expression; D005787:Gene Frequency; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012307:Risk Factors; D013223:Statistics as Topic
D048868:Adaptor Proteins, Signal Transducing; D005819:Genetic Markers; C099942:NEDD9 protein, human; D010750:Phosphoproteins