TY - JOUR
T1 - A full genome scan for late onset Alzheimer's disease
AU - Kehoe, Patrick
AU - Wavrant-De Vrieze, Fabienne
AU - Crook, Richard
AU - Wu, William S.
AU - Holmans, Peter
AU - Fenton, Iain
AU - Spurlock, Gillian
AU - Norton, Nadine
AU - Williams, Hywel
AU - Williams, Nigel
AU - Lovestone, Simon
AU - Perez-Tur, Jordi
AU - Hutton, Mike
AU - Chartier-Harlin, Marie Christine
AU - Shears, Shantia
AU - Roehl, Kimberly
AU - Booth, Jeremy
AU - Van Voorst, Wendy
AU - Ramic, Dzanan
AU - Williams, Julie
AU - Goate, Alison
AU - Hardy, John
AU - Owen, Michael J.
PY - 1999
Y1 - 1999
N2 - We have genotyped 292 affected sibling pairs (ASPs) with Alzheimer's disease (AD) according to NINCDS-ADRDA diagnostic criteria and with onset ages of ≥ 65 years using 237 microsatellite markers separated by an average distance of 16.3 cM. Data were analysed by SPLINK and MAPMAKER/SIBS on the whole sample of 292 ASPs and subsets of 162 ASPs where both members possessed an apolipoprotein E (APOE) ε4 allele and 63 pairs where neither possessed an ε4 allele. Sixteen peaks with a multipoint lod score (MLS) > 1 either in the whole sample, the ε4-positive or -negative subgroups were observed on chromosomes 1 (two peaks), 2, 5, 6, 9 (two peaks), 10 (two peaks), 12, 13, 14, 19, 21 and X (two peaks). Simulation studies revealed that these findings exceeded those expected by chance, although many are likely to be false positives. The highest lod scores on chromosomes 1 (MLS 2.67), 9 (MLS 2.38), 10 (MLS 2.27) and 19 (MLS 1.79) fulfil Lander and Kruglyak's definition of 'suggestive' in that they would be expected to occur by chance once or less per genome scan. Several other peaks were only marginally less significant than this, in particular those on chromosomes 14 (MLS 2.16), 5 (MLS 2.00), 12, close to α2-macroglobulin (MLS 1.91), and 21, close to amyloid precursor protein (MLS 1.77). This is the largest genome scan to date in AD and shows for the first time that this is a genetically complex disorder involving several, perhaps many, genes in addition to APOE. Moreover, our data will be of interest to those hoping to identify positional candidate genes using information emerging from neurobiological studies of AD.
AB - We have genotyped 292 affected sibling pairs (ASPs) with Alzheimer's disease (AD) according to NINCDS-ADRDA diagnostic criteria and with onset ages of ≥ 65 years using 237 microsatellite markers separated by an average distance of 16.3 cM. Data were analysed by SPLINK and MAPMAKER/SIBS on the whole sample of 292 ASPs and subsets of 162 ASPs where both members possessed an apolipoprotein E (APOE) ε4 allele and 63 pairs where neither possessed an ε4 allele. Sixteen peaks with a multipoint lod score (MLS) > 1 either in the whole sample, the ε4-positive or -negative subgroups were observed on chromosomes 1 (two peaks), 2, 5, 6, 9 (two peaks), 10 (two peaks), 12, 13, 14, 19, 21 and X (two peaks). Simulation studies revealed that these findings exceeded those expected by chance, although many are likely to be false positives. The highest lod scores on chromosomes 1 (MLS 2.67), 9 (MLS 2.38), 10 (MLS 2.27) and 19 (MLS 1.79) fulfil Lander and Kruglyak's definition of 'suggestive' in that they would be expected to occur by chance once or less per genome scan. Several other peaks were only marginally less significant than this, in particular those on chromosomes 14 (MLS 2.16), 5 (MLS 2.00), 12, close to α2-macroglobulin (MLS 1.91), and 21, close to amyloid precursor protein (MLS 1.77). This is the largest genome scan to date in AD and shows for the first time that this is a genetically complex disorder involving several, perhaps many, genes in addition to APOE. Moreover, our data will be of interest to those hoping to identify positional candidate genes using information emerging from neurobiological studies of AD.
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U2 - 10.1093/hmg/8.2.237
DO - 10.1093/hmg/8.2.237
M3 - Article
C2 - 9931331
AN - SCOPUS:0032899712
SN - 0964-6906
VL - 8
SP - 237
EP - 245
JO - Human molecular genetics
JF - Human molecular genetics
IS - 2
ER -