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

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

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Case-Control Studies
  • Clusterin / genetics*
  • European Continental Ancestry Group
  • Follow-Up Studies
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Monomeric Clathrin Assembly Proteins / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Complement 3b / genetics*
  • Residence Characteristics

Substances

  • CLU protein, human
  • CR1 protein, human
  • Clusterin
  • Monomeric Clathrin Assembly Proteins
  • PICALM protein, human
  • Receptors, Complement 3b