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Science 22 December 2000:
Vol. 290. no. 5500, pp. 2304 - 2305
DOI: 10.1126/science.290.5500.2304
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Reports

Susceptibility Locus for Alzheimer's Disease on Chromosome 10 

Amanda Myers,1 Peter Holmans,1* Helen Marshall,1 Jennifer Kwon,1 David Meyer,1 Dzanan Ramic,1 Shantia Shears,1 Jeremy Booth,1 Fabienne Wavrant DeVrieze,2 Richard Crook,2 Marian Hamshere,3 Richard Abraham,3 Nigel Tunstall,4 Francis Rice,3 Stephanie Carty,3 Sara Lillystone,3 Pat Kehoe,3 Varuni Rudrasingham,3 Lesley Jones,3 Simon Lovestone,4 Jordi Perez-Tur,5 Julie Williams,3 Michael J. Owen,3 John Hardy,2 Alison M. Goate1dagger

The apolipoprotein E (APOE) gene is the only genetic risk factor that has so far been linked to risk for late-onset Alzheimer's disease (LOAD). However, 50 percent of Alzheimer's disease cases do not carry an APOE4 allele, suggesting that other risk factors must exist. We performed a two-stage genome-wide screen in sibling pairs with LOAD to detect other susceptibility loci. Here we report evidence for an Alzheimer's disease locus on chromosome 10. Our stage one multipoint lod score (logarithm of the odds ratio for linkage/no linkage) of 2.48 (266 sibling pairs) increased to 3.83 in stage 2 (429 sibling pairs) close to D10S1225 (79 centimorgans). This locus modifies risk for Alzheimer's disease independent of APOE genotype.

1 Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
2 Laboratory for Neurogenetics, Birdsall Building, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA.
3 Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK.
4 Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE58AF, UK.
5 Unitat de Genètica Molecular, Institut de Biomedicina de València-CSIC, E-46010 València, Spain.
*   Present address: MRC Biostatistics Unit, Institute of Public Health, Cambridge CB2 2SR, UK.

dagger    To whom correspondence should be addressed. E-mail: goate{at}icarus.wustl.edu

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