Replication of CLU, CR1, and PICALM Associations With Alzheimer Disease

Objective: To test for replication of the association between variants in the CLU, CR1, and PICALM genes with Alzheimer disease. Design: Follow-up case-control association study. Setting: The Mayo Clinics at Jacksonville, Florida, and Rochester, Minnesota. Participants: Community-based patients of European descent with late-onset Alzheimer disease (LOAD) and controls without dementia who were seen at the Mayo clinics, and autopsy-confirmed cases and controls whose pathology was evaluated at the Mayo Clinic in Jacksonville. Additional samples were obtained from the National Cell Repository for Alzheimer Disease (NCRAD). A total of 1829 LOAD cases and 2576 controls were analyzed. Interventions: The most significant single-nucleotide polymorphisms in CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179) were tested for allelic association with LOAD. Main Outcome Measure: Clinical or pathology-confirmed diagnosis of LOAD. Results: Odds ratios for CLU, CR1, and PICALM were 0.82, 1.15, and 0.80, respectively, comparable in direction and magnitude with those originally reported. P values were 8.6 X 10(-5),.014, and 1.3 X 10(-5), respectively; they remain significant even after Bonferroni correction for the 3 single-nucleotide polymorphisms tested. Conclusion: These results show near-perfect replication and provide the first additional evidence that CLU, CR1, and PICALM are associated with the risk of LOAD.