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Replication of CLU, CR1, and PICALM associations with alzheimer disease.


ABSTRACT: To test for replication of the association between variants in the CLU, CR1, and PICALM genes with Alzheimer disease.Follow-up case-control association study.The Mayo Clinics at Jacksonville, Florida, and Rochester, Minnesota.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.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.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.These results show near-perfect replication and provide the first additional evidence that CLU, CR1, and PICALM are associated with the risk of LOAD.

SUBMITTER: Carrasquillo MM 

PROVIDER: S-EPMC2919638 | BioStudies | 2010-01-01

REPOSITORIES: biostudies

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