Journal
AMERICAN JOURNAL OF MEDICAL GENETICS
Volume 114, Issue 2, Pages 235-244Publisher
WILEY-LISS
DOI: 10.1002/ajmg.10183
Keywords
genome screen; genome scan; late-onset Alzheimer disease
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Funding
- NIA NIH HHS [AG16208, U24 AG021886] Funding Source: Medline
- NIMH NIH HHS [U01 MH46281, U01 MH46373, U01 MH46290] Funding Source: Medline
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We performed a two-stage genome screen to search for novel risk factors for late-onset Alzheimer disease (AD). The first stage involved genotyping 292 affected sibling pairs using 237 markers spaced at approximately 20 cM intervals throughout the genome. In the second stage, we genotyped 451 affected sibling pairs (ASPs) with an additional 91 markers, in the 16 regions where the multipoint LOD score was greater than 1 in stage I. Ten regions maintained LOD scores in excess of 1 in stage II, on chromosomes 1 (peak B), 5, 6, 9 (peaks A and B), 10, 12, 19, 21, and X. Our strongest evidence for linkage was on chromosome 10, where we obtained a peak multipoint LOD score (MLS) of 3.9. The linked region on chromosome 10 spans approximately 44 cM from D10S1426 (59 cM) to D10S2327 (103 cM). To narrow this region, we tested for linkage disequilibrium with several of the stage II microsatellite markers. Of the seven markers we tested in family-based and case control samples, the only nominally positive association we found was with the 167 bp allele of marker D10S1217 (chi-square = 7.11, P = 0.045, df = 1). (C) 2002 Wiley-Liss, Inc.
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