Replication of CLU, CR1 and PICALM associations with Alzheimer’s 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 × 10 −5 , .014, and 1.3 × 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.