title: Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease.
abstract: 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).
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Minerva M
authors.initials: MM
authors.lastname: Carrasquillo
authors.forename: Fanggeng
authors.initials: F
authors.lastname: Zou
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Wilcox
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Louise P
authors.initials: LP
authors.lastname: Walker
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Younkin
authors.forename: Curtis S
authors.initials: CS
authors.lastname: Younkin
authors.forename: Linda H
authors.initials: LH
authors.lastname: Younkin
authors.forename: Gina D
authors.initials: GD
authors.lastname: Bisceglio
authors.forename: Nilufer
authors.initials: N
authors.lastname: Ertekin-Taner
authors.forename: Julia E
authors.initials: JE
authors.lastname: Crook
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: Steven G
authors.initials: SG
authors.lastname: Younkin
mesh_terms: 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
chemical_list: D015820:Cadherins; C404498:PCDH11X protein, human; D000091363:Protocadherins