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

Blom, Elin S., Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Arepalli, Sampath, Adighibe, Omanma, Hamshere, Marian Lindsay ORCID: https://orcid.org/0000-0002-8990-0958, Gatz, Margaret, Pedersen, Nancy L., Bergem, A. L. Mina, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Hollingworth, Paul, Goate, Alison, Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259, Lannfelt, Lars, Hardy, John, Wavrant-De Vrièze, Fabienne and Glaser, Anna 2008. Does APOE explain the linkage of Alzheimer's disease to chromosome 19q13? American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 147B (6) , pp. 778-783. 10.1002/ajmg.b.30681

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Abstract

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 ε4 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Alzheimer’s disease, APOE, linkage, age at onset, polipoprotein E
Publisher:	John Wiley & Sons inc.
ISSN:	1552-4841
Last Modified:	19 Oct 2022 09:45
URI:	https://orca.cardiff.ac.uk/id/eprint/22114

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