Expanded high-resolution genetic study of 109 Swedish families with Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disease that affects approximately 20 million persons all over the world. There are both sporadic and familial forms of AD. We have previously reported a genome-wide linkage analysis on 71 Swedish AD families using 365 genotyped microsatellite markers. In this study, we increased the number of individuals included in the original 71 analysed families besides adding 38 new families. These 109 families were genotyped for 1100 novel microsatellite markers. The present study reports on the linkage data generated from the non-overlapping genotypes from the first genome scan and the genotypes of the present scan, which results in a total of 1289 successfully genotyped markers at an average density of 2.85 cM on 468 individuals from 109 AD families. Non-parametric linkage analysis yielded a significant multipoint LOD score in chromosome 19q13, the region harbouring the major susceptibility gene APOE, both for the whole set of families (LOD=5.0) and the APOE varepsilon4-positive subgroup made up of 63 families (LOD=5.3). Other suggestive linkage peaks that were observed in the original genome scan of 71 Swedish AD families were not detected in this extended analysis, and the previously reported linkage signals in chromosomes 9, 10 and 12 were not replicated.
Sillén
Anna
A
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet Dainippon Sumitomo Pharma Alzheimer Center (KASPAC), Karolinska Institutet, Huddinge, Sweden.
Andrade
Jorge
J
Lilius
Lena
L
Forsell
Charlotte
C
Axelman
Karin
K
Odeberg
Jacob
J
Winblad
Bengt
B
Graff
Caroline
C
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D013548:Sweden
D001057:Apolipoproteins E; D005819:Genetic Markers