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Susceptibility Locus for Alzheimer's Disease on Chromosome 10

Science  22 Dec 2000:
Vol. 290, Issue 5500, pp. 2304-2305
DOI: 10.1126/science.290.5500.2304

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Abstract

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 ofAPOE genotype.

  • * Present address: MRC Biostatistics Unit, Institute of Public Health, Cambridge CB2 2SR, UK.

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

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