Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer's disease

Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Hamshere, Marian Lindsay ORCID: https://orcid.org/0000-0002-8990-0958, Hollingworth, P., Rice, Frances ORCID: https://orcid.org/0000-0002-9484-1729, Tunstall, N., Jones, S., Moore, P., Wavrant DeVrieze, F., Myers, A., Crook, R., Compton, D., Marshall, H., Meyer, D., Shears, S., Booth, J., Ramic, D., Williams, Nigel Melville ORCID: https://orcid.org/0000-0003-1177-6931, Norton, N., Abraham, R., Kehoe, P., Williams, H., Rudrasingham, V., O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Jones, Lesley ORCID: https://orcid.org/0000-0002-3007-4612, Hardy, J., Goate, A., Lovestone, S., Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 and Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259 2005. Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 135B (1) , pp. 24-32. 10.1002/ajmg.b.30114

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Abstract

We performed an affected sib-pair (ASP) linkage analysis to test for the effects of age at onset (AAO), rate of decline (ROD), and Apolipoprotein E (APOE) genotype on linkage to late-onset Alzheimer's disease (AD) in a sample comprising 428 sib-pairs. We observed linkage of mean AAO to chromosome 21 in the whole sample (max LOD = 2.57). This came entirely from the NIMH sample (max LOD = 3.62), and was strongest in pairs with high mean AAO (>80). A similar effect was observed on chromosome 2q in the NIMH sample (max LOD = 2.73); this region was not typed in the IADC/UK sample. Suggestive evidence was observed in the combined sample of linkage of AAO difference to chromosome 19q (max LOD = 2.33) in the vicinity of APOE and 12p (max LOD = 2.22), with linkage strongest in sib-pairs with similar AAO. Mean ROD showed suggestive evidence of linkage to chromosome 9q in the whole sample (max LOD = 2.29), with the effect strongest in the NIMH sample (max LOD = 3.58), and in pairs with high mean ROD. Additional suggestive evidence was also observed in the NIMH sample with AAO difference on chromosome 6p (max LOD = 2.44) and 15p (max LOD = 1.87), with linkage strongest in pairs with similar AAO, and in the UK sample with mean ROD on chromosome 1p (max LOD = 2.73, linkage strongest in pairs with high mean ROD). We also observed suggestive evidence of increased identical by descent (IBD) in APOE epsilon4 homozygotes on chromosome 1 (max LOD = 3.08) and chromosome 9 (max LOD = 3.34). The previously reported genome-wide linkage of AD to chromosome 10 was not influenced by any of the covariates studied.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Wiley-Blackwell
ISSN:	1552-4841
Last Modified:	04 Mar 2023 03:04
URI:	https://orca.cardiff.ac.uk/id/eprint/83490

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