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Randomized Controlled Trial
. 2010 Aug;67(8):961-4.
doi: 10.1001/archneurol.2010.147. Epub 2010 Jun 14.

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

Minerva M Carrasquillo  1 , Olivia Belbin, Talisha A Hunter, Li Ma, Gina D Bisceglio, Fanggeng Zou, Julia E Crook, V Shane Pankratz, Dennis W Dickson, Neill R Graff-Radford, Ronald C Petersen, Kevin Morgan, Steven G Younkin
Affiliations
Randomized Controlled Trial

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

Minerva M Carrasquillo et al. Arch Neurol. 2010 Aug.

Abstract

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.

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