Full genome screen for Alzheimer disease: Stage II analysis

Amanda Myers, Fabienne Wavrant De-Vrieze, Peter Holmans, Marian Hamshere, Richard Crook, Danielle Compton, Helen Marshall, David Meyer, Shantia Shears, Jeremy Booth, Dzanan Ramic, Heather Knowles, John C. Morris, Nigel Williams, Nadine Norton, Richard Abraham, Pat Kehoe, Hywel Williams, Varuni Rudrasingham, Francis RicePeter Giles, Nigel Tunstall, Lesley Jones, Simon Lovestone, Julie Williams, Michael J. Owen, John Hardy, Alison Goate

Research output: Contribution to journalArticle

179 Scopus citations

Abstract

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).

Original languageEnglish (US)
Pages (from-to)235-244
Number of pages10
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume114
Issue number2
DOIs
StatePublished - Mar 8 2002

Keywords

  • Genome scan
  • Genome screen
  • Late-onset Alzheimer disease

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

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    Myers, A., De-Vrieze, F. W., Holmans, P., Hamshere, M., Crook, R., Compton, D., Marshall, H., Meyer, D., Shears, S., Booth, J., Ramic, D., Knowles, H., Morris, J. C., Williams, N., Norton, N., Abraham, R., Kehoe, P., Williams, H., Rudrasingham, V., ... Goate, A. (2002). Full genome screen for Alzheimer disease: Stage II analysis. American Journal of Medical Genetics - Neuropsychiatric Genetics, 114(2), 235-244. https://doi.org/10.1002/ajmg.10183