SORL1 is genetically associated with increased risk for late-onset Alzheimer disease in the Belgian population

SORL1 has recently been identified as a major genetic contributor to increased risk for late-onset Alzheimer disease (AD). Here we aimed at replicating this finding in a large, well-characterized group of 550 Belgian late-onset AD patients and 637 healthy control individuals using a gene-wide genotyping approach across the SORL1 locus. We observed significant associations, both for individual SNPs (SNPs 6, 8, 9, 10 and 27; p-values ranging from 0.001 to 0.040) and 3-SNP haplotypes (SNPs 5-6-7 and SNPs 25-26-27; p-values ranging from 0.008 to 0.035). Moreover, the associations at SNP 8, 9 and 10 represented a direct replication of the initial association data. Two signals in distinct regions of the gene were shown to be mutually independent, supporting allelic heterogeneity at the SORL1 locus in the Belgian population. Our findings confirm that genetic variants in SORL1 may be important risk factors for late-onset AD. (C) 2008 Wiley-Liss.