INITIAL RESULTS OF A GENOME SURVEY FOR NOVEL ALZHEIMERS-DISEASE RISK GENES - ASSOCIATION WITH A LOCUS ON THE X-CHROMOSOME

As the initial step in a systematic genome survey, 16 simple sequence tandem repeat polymorphisms that span the X chromosome at an average s pacing of 10 cM were examined for allelic associations with typical-on set Alzheimer's disease (AD), The efficiency of this survey was substa ntially enhanced by genotyping pools of genomic DNA from 50 autopsy-co nfirmed AD cases and 50 autopsied controls who were similar in sex rat io, race, and age at death, The frequency of the DXS1047 202-bp allele was twice as common among AD cases (0.45 +/- S.E. 0.06) than controls (0.22 +/- S.E. 0.05), a finding that was reproduced in an independent and geographically disparate sample, Consistent with Hardy-Weinberg e quilibrium, the proportion of women with AD who carried the 202-bp all ele, 73% was nearly double that observed for men with AD, 38%. However , the frequency of the 202-bp allele was similar for men and women and the presence of this allele did not affect the age at onset of dement ia in either sex, Furthermore, the frequency of the DXS1047 202-bp all ele in AD cases and controls was unaffected by the APOE genotype, indi cating that these two loci modulate AD risk independently, Finally, th e frequency of the 202-bp allele among 50 autopsy-confirmed cases of P arkinson's disease (0.29 +/- S.E. 0.06) was indistinguishable from the control value, reflecting relative specificity for this allelic assoc iation with AD. (C) 1998 Wiley-Liss, Inc.