Identification of novel loci for Alzheimer disease and replication of CLU, PICALM, and BIN1 in Caribbean Hispanic individuals

Arch Neurol. 2011 Mar;68(3):320-8. doi: 10.1001/archneurol.2010.292. Epub 2010 Nov 8.

Abstract

Objectives: To identify novel loci for late-onset Alzheimer disease (LOAD) in Caribbean Hispanic individuals and to replicate the findings in a publicly available data set from the National Institute on Aging Late-Onset Alzheimer's Disease Family Study.

Design: Nested case-control genome-wide association study.

Setting: The Washington Heights-Inwood Columbia Aging Project and the Estudio Familiar de Influencia Genetica de Alzheimer study.

Participants: Five hundred forty-nine affected and 544 unaffected individuals of Caribbean Hispanic ancestry.

Intervention: The Illumina HumanHap 650Y chip for genotyping.

Main outcome measure: Clinical diagnosis or pathologically confirmed diagnosis of LOAD.

Results: The strongest support for allelic association was for rs9945493 on 18q23 (P=1.7×10(-7)), but 22 additional single-nucleotide polymorphisms (SNPs) had a P value less than 9×10(-6) under 3 different analyses: unadjusted and stratified by the presence or absence of the APOE ε4 allele. Of these SNPs, 5 SNPs (rs4669573 and rs10197851 on 2p25.1; rs11711889 on 3q25.2; rs1117750 on 7p21.1; and rs7908652 on 10q23.1) were associated with LOAD in an independent cohort from the National Institute on Aging Late-Onset Alzheimer's Disease Family Study. We also replicated genetic associations for CLU, PICALM, and BIN1.

Conclusions: Our genome-wide search of Caribbean Hispanic individuals identified several novel genetic variants associated with LOAD and replicated these associations in a white cohort. We also replicated associations in CLU, PICALM, and BIN1 in the Caribbean Hispanic cohort.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / psychology
  • Apolipoproteins E / genetics
  • Blacks
  • Caribbean Region
  • Clusterin / genetics*
  • Cohort Studies
  • Data Interpretation, Statistical
  • Female
  • Gene Frequency
  • Genome-Wide Association Study
  • Genotype
  • Hispanic or Latino
  • Humans
  • Male
  • Monomeric Clathrin Assembly Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Tumor Suppressor Proteins / genetics*
  • Whites

Substances

  • Adaptor Proteins, Signal Transducing
  • Apolipoproteins E
  • BIN1 protein, human
  • CLU protein, human
  • Clusterin
  • Monomeric Clathrin Assembly Proteins
  • Nuclear Proteins
  • PICALM protein, human
  • Tumor Suppressor Proteins