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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.

Original publication

DOI

10.1126/science.290.5500.2304

Type

Journal article

Journal

Science

Publication Date

22/12/2000

Volume

290

Pages

2304 - 2305

Keywords

Age of Onset, Aged, Alleles, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Chromosomes, Human, Pair 10, Genetic Linkage, Genetic Markers, Genetic Predisposition to Disease, Genotype, Humans, Lod Score, Nuclear Family, Odds Ratio