Harold et al. and Lambert et al. recently published two large genome-wide association studies of late onset Alzheimer’s disease (LOAD) in which CLU, CR1, and PICALM were identified as novel LOAD genes.
To test for replication of the association between variants in the CLU, CR1 and PICALM genes with Alzheimer’s disease.
Case-control association study
Community-based ascertainment of patients seen at the Mayo Clinic Jacksonville, FL and Rochester, MN, and autopsy-confirmed cases and controls whose pathology was evaluated at the Mayo Clinic Jacksonville. Additional samples were obtained from the National Cell Repository for Alzheimer’s Disease (NCRAD).
LOAD case-control series of European descent consisting of 1,829 LOAD cases and 2,576 controls
Main Outcome Measure
Clinical or pathology-confirmed diagnosis of LOAD
In our follow-up study of 1,829 LOAD cases and 2,576 controls, the most significant SNPs in CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179) were tested for allelic association and gave ORs of 0.82, 1.15, and 0.80 respectively that were comparable in direction and magnitude to those originally reported with p values of 8.6×10−5, 0.014, and 1.3×10−5 that were significant even after Bonferroni correction for 3 SNPs tested.
These results showing near perfect replication provide the first additional evidence that CLU, CR1, and PICALM are LOAD genes.