Identification of Novel Loci for Alzheimer Disease and Replication of CLU, PICALM, and BIN1 in Caribbean Hispanic Individuals

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 X 10(-7)), but 22 additional single-nucleotide polymorphisms (SNPs) had a P value less than 9 X 10(-6) under 3 different analyses: unadjusted and stratified by the presence or absence of the APOE 64 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.