A GENOME SURVEY FOR NOVEL ALZHEIMER-DISEASE RISK LOCI - RESULTS AT 10-CM RESOLUTION

We completed a systematic survey of the human genome, conducted at an average resolution of 10 cM, for the identification of simple sequence tandem repeat polymorphisms (SSTRPs) that target new risk genes for A lzheimer disease (AD) by virtue of linkage disequilibrium. The efficie ncy of our association study was enhanced by genotyping pools of DNA f rom autopsy-confirmed cases with AD and matched controls. Allelic asso ciations with AD were observed for 6 of the 391 SSTRPs in the CHLC Hum an Screening Set/Weber Version 6 (Research Genetics, Inc., Huntsville, AL): D1S518, D1S5547, D10S1423, D12S1045, D19S178, and DXS1047. These allelic associations were replicated in an independent sample of auto psied AD cases and controls recruited from a geographically disparate site. The association of the large D19S178 alleles with AD appeared to arise from Linkage disequilibrium with the APOE epsilon 4 allele, who se effect on increasing the risk of AD has been established. None of t he remaining SSTRPs was in close proximity to loci previously reported to influence the risk of developing AD. Instead, they may identify fi ve novel AD susceptibility loci. (C) 1998 Academic Press.