A genome-wide linkage analysis of dementia in the Amish

Susceptibility genes for Alzheimer's disease are proving to be highly challenging to detect and verify. Population heterogeneity may be a significant confounding factor contributing to this difficulty. To increase the power for disease susceptibility gene detection we conducted a genome-wide genetic linkage screen using individuals from the relatively isolated, genetically homogeneous, Amish population. Our genome linkage analysis used a 407 microsatellite marker map (average density 7 cM) to search for autosomal genes linked to dementia in five Amish families from four Midwestern U.S. counties. Our highest two-point lod score (3.01) was observed at marker D4S1548 on chromosome 4q31. Five other regions (10q22, 3q28, 11p13, 4q28, 19p13) also demonstrated suggestive linkage with markers having two-point lod scores >2.0. While two of these regions are novel (4q31 and 11p13), the other regions lie close to regions identified in previous genome scans in other populations. Our results identify regions of the genome that may harbor genes involved in a subset of dementia patients, in particular the North American Amish community.