title: Full genome screen for Alzheimer disease: stage II analysis.
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).
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Myers
authors.forename: Fabienne
authors.initials: F
authors.lastname: Wavrant De-Vrieze
authors.forename: Peter
authors.initials: P
authors.lastname: Holmans
authors.forename: Marian
authors.initials: M
authors.lastname: Hamshere
authors.forename: Richard
authors.initials: R
authors.lastname: Crook
authors.forename: Danielle
authors.initials: D
authors.lastname: Compton
authors.forename: Helen
authors.initials: H
authors.lastname: Marshall
authors.forename: David
authors.initials: D
authors.lastname: Meyer
authors.forename: Shantia
authors.initials: S
authors.lastname: Shears
authors.forename: Jeremy
authors.initials: J
authors.lastname: Booth
authors.forename: Dzanan
authors.initials: D
authors.lastname: Ramic
authors.forename: Heather
authors.initials: H
authors.lastname: Knowles
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Nigel
authors.initials: N
authors.lastname: Williams
authors.forename: Nadine
authors.initials: N
authors.lastname: Norton
authors.forename: Richard
authors.initials: R
authors.lastname: Abraham
authors.forename: Pat
authors.initials: P
authors.lastname: Kehoe
authors.forename: Hywel
authors.initials: H
authors.lastname: Williams
authors.forename: Varuni
authors.initials: V
authors.lastname: Rudrasingham
authors.forename: Francis
authors.initials: F
authors.lastname: Rice
authors.forename: Peter
authors.initials: P
authors.lastname: Giles
authors.forename: Nigel
authors.initials: N
authors.lastname: Tunstall
authors.forename: Lesley
authors.initials: L
authors.lastname: Jones
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.forename: Julie
authors.initials: J
authors.lastname: Williams
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats