Does APOE explain the linkage of Alzheimer's disease to chromosome 19q13?
We have studied the impact of the apolipoprotein E gene (APOE) on the chromosome 19 linkage peak from an analysis of sib-pairs affected by Alzheimer's disease. We genotyped 417 affected sib-pairs (ASPs) collected in Sweden and Norway (SWE), the UK and the USA for 10 microsatellite markers on chromosome 19. The highest Zlr (3.28, chromosome-wide P-value 0.036) from the multipoint linkage analysis was located approximately 1 Mb from APOE, at marker D19S178. The linkage to chromosome 19 was well explained by APOE in the whole sample as well as in the UK and USA subsamples, as identity by descent (IBD) increased with the number of epsilon4 alleles in ASPs. There was a suggestion from the SWE subsample that linkage was higher than would be expected from APOE alone, although the test for this did not reach formal statistical significance. There was also a significant age at onset (aao) effect on linkage to chromosome 19q13 in the whole sample, which manifested itself as increased IBD sharing in relative pairs with lower mean aao. This effect was partially, although not completely, explained by APOE. The aao effect varied considerably between the different subsamples, with most of the effect coming from the UK sample. The other samples showed smaller effects in the same direction, but these were not significant.
Blom
Elin S
ES
Section of Molecular Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden. elin.blom@pubcare.uu.se
Holmans
Peter
P
Arepalli
Sampath
S
Adighibe
Omanma
O
Hamshere
Marian L
ML
Gatz
Margaret
M
Pedersen
Nancy L
NL
Bergem
A L Mina
AL
Owen
Michael J
MJ
Hollingworth
Paul
P
Goate
Alison
A
Williams
Julie
J
Lannfelt
Lars
L
Hardy
John
J
Wavrant-De Vrièze
Fabienne
F
Glaser
Anna
A
D017668:Age of Onset; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D005190:Family; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D014427:Twins; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
D001057:Apolipoproteins E