Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease.
Late-onset Alzheimer's disease (LOAD) is a genetically complex neurodegenerative disorder. Currently, only the epsilon4 allele of the Apolipoprotein E gene has been identified unequivocally as a genetic susceptibility factor for LOAD. Others remain to be found. In 2002 we observed genome-wide significant evidence of linkage to a region on chromosome 10q11.23-q21.3 [Myers et al. (2002) Am J Med Genet 114:235-244]. Our objective in this study was to test every gene within the maximum LOD-1 linkage region, for association with LOAD. We obtained results for 528 SNPs from 67 genes, with an average density of 1 SNP every 10 kb within the genes. We demonstrated nominally significant association with LOAD for 4 SNPs: rs1881747 near DKK1 (P = 0.011, OR = 1.24), rs2279420 in ANK3 (P = 0.022, OR = 0.79), rs2306402 in CTNNA3 (P = 0.024, OR = 1.18), and rs5030882 in CXXC6 (P = 0.046, OR = 1.29) in 1,160 cases and 1,389 controls. These results would not survive correction for multiple testing but warrant attempts at confirmation in independent samples.
Morgan
A R
AR
Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK. morganar1@cardiff.ac.uk
Hamilton
G
G
Turic
D
D
Jehu
L
L
Harold
D
D
Abraham
R
R
Hollingworth
P
P
Moskvina
V
V
Brayne
C
C
Rubinsztein
D C
DC
Lynch
A
A
Lawlor
B
B
Gill
M
M
O'Donovan
M
M
Powell
J
J
Lovestone
S
S
Williams
J
J
Owen
M J
MJ
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D017487:Ankyrins / Q000235:genetics; D016022:Case-Control Studies; D002879:Chromosomes, Human, Pair 10; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051178:alpha Catenin / Q000235:genetics
C490613:ANK3 protein, human; D017487:Ankyrins; C441963:CTNNA3 protein, human; C501126:DKK1 protein, human; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D051178:alpha Catenin; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human