Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease.

TitleGenetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2009
AuthorsCarrasquillo MM, Zou F, V Pankratz S, Wilcox SL, Ma L, Walker LP, Younkin SG, Younkin CS, Younkin LH, Bisceglio GD, Ertekin-Taner N, Crook JE, Dickson DW, Petersen RC, Graff-Radford NR, Younkin SG
JournalNat Genet
Volume41
Issue2
Pagination192-8
Date Published2009 Feb
ISSN1546-1718
KeywordsAge of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Cadherins, Case-Control Studies, Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Heterozygote, Humans, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide
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).

DOI10.1038/ng.305
Alternate JournalNat. Genet.
PubMed ID19136949
PubMed Central IDPMC2873177
Grant ListP50 AG16574 / AG / NIA NIH HHS / United States
R01 AG018023-07 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
P50 AG016574 / AG / NIA NIH HHS / United States
P50 AG025711-019003 / AG / NIA NIH HHS / United States
P50 AG016574-100006 / AG / NIA NIH HHS / United States
F32 AG020903 / AG / NIA NIH HHS / United States
U01 AG06576 / AG / NIA NIH HHS / United States
P01 AG003949-200009 / AG / NIA NIH HHS / United States
AG12716 / AG / NIA NIH HHS / United States
AG25711 / AG / NIA NIH HHS / United States
R01 AG18023 / AG / NIA NIH HHS / United States
P01 AG003949 / AG / NIA NIH HHS / United States
U01 AG006786-19 / AG / NIA NIH HHS / United States
U24 AG21886 / AG / NIA NIH HHS / United States
P50 AG025711 / AG / NIA NIH HHS / United States
F32 AG020903-02 / AG / NIA NIH HHS / United States
P01 AG017216 / AG / NIA NIH HHS / United States
P01 AG017216-019001 / AG / NIA NIH HHS / United States
R01 AG018023 / AG / NIA NIH HHS / United States
U24 AG021886-02 / AG / NIA NIH HHS / United States
U01 AG006786 / AG / NIA NIH HHS / United States
AG03949 / AG / NIA NIH HHS / United States