title: Replication of EPHA1 and CD33 associations with late-onset Alzheimer's disease: a multi-centre case-control study.
abstract: BACKGROUND
  A recently published genome-wide association study (GWAS) of late-onset Alzheimer's disease (LOAD) revealed genome-wide significant association of variants in or near MS4A4A, CD2AP, EPHA1 and CD33. Meta-analyses of this and a previously published GWAS revealed significant association at ABCA7 and MS4A, independent evidence for association of CD2AP, CD33 and EPHA1 and an opposing yet significant association of a variant near ARID5B. In this study, we genotyped five variants (in or near CD2AP, EPHA1, ARID5B, and CD33) in a large (2,634 LOAD, 4,201 controls), independent dataset comprising six case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and tested for association using logistic regression adjusted by age-at-diagnosis, gender, and APOE ε4 dosage.
  
  
  RESULTS
  We found no significant evidence of series heterogeneity. Associations with LOAD were successfully replicated for EPHA1 (rs11767557; OR = 0.87, p = 5 × 10-4) and CD33 (rs3865444; OR = 0.92, p = 0.049), with odds ratios comparable to those previously reported. Although the two ARID5B variants (rs2588969 and rs494288) showed significant association with LOAD in meta-analysis of our dataset (p = 0.046 and 0.008, respectively), the associations did not survive adjustment for covariates (p = 0.30 and 0.11, respectively). We had insufficient evidence in our data to support the association of the CD2AP variant (rs9349407, p = 0.56).
  
  
  CONCLUSIONS
  Our data overwhelmingly support the association of EPHA1 and CD33 variants with LOAD risk: addition of our data to the results previously reported (total n > 42,000) increased the strength of evidence for these variants, providing impressive p-values of 2.1 × 10-15 (EPHA1) and 1.8 × 10-13 (CD33).
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA. younkin.steven@mayo.edu.
authors.forename: Minerva M
authors.initials: MM
authors.lastname: Carrasquillo
authors.forename: Olivia
authors.initials: O
authors.lastname: Belbin
authors.forename: Talisha A
authors.initials: TA
authors.lastname: Hunter
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Gina D
authors.initials: GD
authors.lastname: Bisceglio
authors.forename: Fanggeng
authors.initials: F
authors.lastname: Zou
authors.forename: Julia E
authors.initials: JE
authors.lastname: Crook
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Sigrid B
authors.initials: SB
authors.lastname: Sando
authors.forename: Jan O
authors.initials: JO
authors.lastname: Aasly
authors.forename: Maria
authors.initials: M
authors.lastname: Barcikowska
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Peter
authors.initials: P
authors.lastname: Passmore
authors.forename: Kevin
authors.initials: K
authors.lastname: Morgan
authors.forename: Steven G
authors.initials: SG
authors.lastname: Younkin