Full genome screen for Alzheimer disease: stage II analysis.
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).
Myers
Amanda
A
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Wavrant De-Vrieze
Fabienne
F
Holmans
Peter
P
Hamshere
Marian
M
Crook
Richard
R
Compton
Danielle
D
Marshall
Helen
H
Meyer
David
D
Shears
Shantia
S
Booth
Jeremy
J
Ramic
Dzanan
D
Knowles
Heather
H
Morris
John C
JC
Williams
Nigel
N
Norton
Nadine
N
Abraham
Richard
R
Kehoe
Pat
P
Williams
Hywel
H
Rudrasingham
Varuni
V
Rice
Francis
F
Giles
Peter
P
Tunstall
Nigel
N
Jones
Lesley
L
Lovestone
Simon
S
Williams
Julie
J
Owen
Michael J
MJ
Hardy
John
J
Goate
Alison
A
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