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- W2747191567 abstract "The only confirmed risk factor gene for late onset Alzheimer's disease (LOAD) is apolipoprotein, and it explains only a modest portion of LOAD. It is necessary to identify additional risk factor genes. Here we update our previous genome scan study by expanding the study with an additional 114 families, for a total of 210 extended families. To identify novel candidate regions for LOAD and to confirm previously identified candidate regions, we conducted a genome scan. We conducted a genome scan using 1,147 family members from 210 late–onset (age≥65) AD Caribbean Hispanic families. We examined 403 microsatellite markers with an intermarker distance of 9.3 cM. In the current genome scan, we conducted linkage analysis using 2 definitions of AD: possible and probable AD. We first performed affected–only 2–point linkage analysis under the autosomal dominant and recessive models. Subsequently, we conducted multipoint affected sibpair (ASP) linkage analysis. In addition, we conducted a simulation experiment to estimate genome wide empirical p–values to control for multiple testing. For possible AD, our two–point parametric linkage analysis identified several regions that were significant at the genome–wide empirical p<0.05). The strongest evidence for linkage was observed for 3q28 (LOD=3.09), and additional regions, including 5p15 (LOD =1.87), 9q32 (LOD =1.94), 12q24 (LOD =2.43), 14q22 (LOD =2.53), and 14q23 (LOD =2.16), also showed strong support. For probable AD, many candidate regions overlapped, as expected. However, several additional regions supported linkage, including 2p25.3 (LOD=2.73), 6p21 (LOD =2.18), 7p21 (LOD =2.05). Our multi–point non–parametric affected sib–pair (ASP) linkage analysis confirmed most loci that were identified by the two–point parametric linkage analysis. In addition, for probable AD, we identified a susceptibility locus at 2q34 (LOD = 2.75) that was not significant in the two–point analysis. In the current genome scan, we identified six novel loci (namely 2p25.3, 2q34, 3q28, 7p21, 9q32 and 12q24), and confirmed four loci that were identified in previous studies (namely 5p15, 6p21, 14q22 and 14q23)." @default.
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- W2747191567 date "2006-07-01" @default.
- W2747191567 modified "2023-10-18" @default.
- W2747191567 title "O2-02-04: A genomewide screen of 210 extended caribbean hispanic families with late-onset Alzheimer's disease" @default.
- W2747191567 doi "https://doi.org/10.1016/j.jalz.2006.05.114" @default.
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