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Full genome screen for Alzheimer disease: stage II analysis
Amanda Myers1, Fabienne Wavrant De-Vrieze, Peter Holmans
1Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
American Journal of Medical Genetics
|February 22, 2002
Summary
This study identified novel genetic regions associated with late-onset Alzheimer disease (AD). The strongest linkage was found on chromosome 10, suggesting new risk factors for AD.
Area of Science:
- Genetics
- Neuroscience
- Medical Research
Background:
- Late-onset Alzheimer disease (AD) poses a significant public health challenge.
- Identifying novel genetic risk factors is crucial for understanding AD pathogenesis.
- Genome-wide screens are powerful tools for discovering susceptibility genes.
Purpose of the Study:
- To conduct a two-stage genome screen to identify novel genetic risk factors for late-onset Alzheimer disease (AD).
- To pinpoint specific chromosomal regions linked to AD susceptibility.
- To investigate potential associations within identified regions using linkage disequilibrium.
Main Methods:
- Utilized a two-stage genome screening approach in affected sibling pairs (ASPs).
- Stage I involved genotyping 292 ASPs with 237 genome-wide markers.
- Stage II focused on 451 ASPs, genotyping additional markers in regions with LOD scores > 1 from Stage I.
Main Results:
- Ten chromosomal regions maintained significant linkage signals (LOD score > 1) in Stage II.
- The strongest evidence for linkage was on chromosome 10 (peak multipoint LOD score [MLS] = 3.9).
- A nominally positive association was observed with the D10S1217 marker on chromosome 10 (P=0.045).
Conclusions:
- The study identified several novel chromosomal regions linked to late-onset Alzheimer disease.
- Chromosome 10 shows the strongest evidence for linkage, warranting further investigation.
- The D10S1217 marker may represent a potential risk factor for Alzheimer disease.