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Does APOE explain the linkage of Alzheimer’s disease to chromosome 19q13?

Blom, Elin Susanne (author)
Uppsala universitet,Geriatrik
Holmans, Peter (author)
Arepalli, Sampath (author)
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Adighibe, Omanma (author)
Hamshere, Marian L. (author)
Gatz, Margaret (author)
Pedersen, Nancy L. (author)
Karolinska Institutet
Bergem, A. L. Mina (author)
Owen, Michael J. (author)
Hollingworth, Paul (author)
Goate, Alison (author)
Williams, Julie (author)
Lannfelt, Lars (author)
Uppsala universitet,Geriatrik
Hardy, John (author)
Wavrant-De Vrièze, Fabienne (author)
Glaser, Anna (author)
Uppsala universitet,Geriatrik
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 (creator_code:org_t)
2007-12-27
2008
English.
In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-485X. ; 147B:6, s. 778-83
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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 multi-point 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 epsilon 4 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.

Keyword

Alzheimer's disease
APOE
linkage
age at onset
apolipoprotein E
MEDICINE
MEDICIN

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ref (subject category)
art (subject category)

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