Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease.
By analyzing late-onset Alzheimer's disease (LOAD) in a genome-wide association study (313,504 SNPs, three series, 844 cases and 1,255 controls) and evaluating the 25 SNPs with the most significant allelic association in four additional series (1,547 cases and 1,209 controls), we identified a SNP (rs5984894) on Xq21.3 in PCDH11X that is strongly associated with LOAD in individuals of European descent from the United States. Analysis of rs5984894 by multivariable logistic regression adjusted for sex gave global P values of 5.7 x 10(-5) in stage 1, 4.8 x 10(-6) in stage 2 and 3.9 x 10(-12) in the combined data. Odds ratios were 1.75 (95% CI = 1.42-2.16) for female homozygotes (P = 2.0 x 10(-7)) and 1.26 (95% CI = 1.05-1.51) for female heterozygotes (P = 0.01) compared to female noncarriers. For male hemizygotes (P = 0.07) compared to male noncarriers, the odds ratio was 1.18 (95% CI = 0.99-1.41).
Carrasquillo
Minerva M
MM
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
Zou
Fanggeng
F
Pankratz
V Shane
VS
Wilcox
Samantha L
SL
Ma
Li
L
Walker
Louise P
LP
Younkin
Samuel G
SG
Younkin
Curtis S
CS
Younkin
Linda H
LH
Bisceglio
Gina D
GD
Ertekin-Taner
Nilufer
N
Crook
Julia E
JE
Dickson
Dennis W
DW
Petersen
Ronald C
RC
Graff-Radford
Neill R
NR
Younkin
Steven G
SG
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000502:physiology; D055106:Genome-Wide Association Study; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000091363:Protocadherins
D015820:Cadherins; C404498:PCDH11X protein, human; D000091363:Protocadherins