TY - JOUR
T1 - Full genome screen for Alzheimer disease
T2 - Stage II analysis
AU - Myers, Amanda
AU - De-Vrieze, Fabienne Wavrant
AU - Holmans, Peter
AU - Hamshere, Marian
AU - Crook, Richard
AU - Compton, Danielle
AU - Marshall, Helen
AU - Meyer, David
AU - Shears, Shantia
AU - Booth, Jeremy
AU - Ramic, Dzanan
AU - Knowles, Heather
AU - Morris, John C.
AU - Williams, Nigel
AU - Norton, Nadine
AU - Abraham, Richard
AU - Kehoe, Pat
AU - Williams, Hywel
AU - Rudrasingham, Varuni
AU - Rice, Francis
AU - Giles, Peter
AU - Tunstall, Nigel
AU - Jones, Lesley
AU - Lovestone, Simon
AU - Williams, Julie
AU - Owen, Michael J.
AU - Hardy, John
AU - Goate, Alison
PY - 2002/3/8
Y1 - 2002/3/8
N2 - 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).
AB - 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).
KW - Genome scan
KW - Genome screen
KW - Late-onset Alzheimer disease
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U2 - 10.1002/ajmg.10183
DO - 10.1002/ajmg.10183
M3 - Article
C2 - 11857588
AN - SCOPUS:18244407351
SN - 1552-4841
VL - 114
SP - 235
EP - 244
JO - American Journal of Medical Genetics - Neuropsychiatric Genetics
JF - American Journal of Medical Genetics - Neuropsychiatric Genetics
IS - 2
ER -