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Familial influence on variation in age of onset and behavioural phenotype in Alzheimer's disease

Tunstall, N., Owen, Michael John, Williams, Julie, Rice, Frances, Carty, S., Lillystone, S., Fraser, L., Kehoe, P., Neill, D., Rudrasingham, V., Sham, P. and Lovestone, S. 2000. Familial influence on variation in age of onset and behavioural phenotype in Alzheimer's disease. British Journal of Psychiatry 176 , pp. 156-159. 10.1192/bjp.176.2.156

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BACKGROUND: Alzheimer's disease manifests considerable heterogeneity, the cause of which is unknown. AIMS: To determine the familial (genotypic) influence on phenomenology (phenotype) in Alzheimer's disease. METHOD: Affected sibling pairs with Alzheimer's disease were assessed for a range of cognitive and non-cognitive symptoms. Resemblance for phenotypic characteristics was estimated using intraclass correlations for continuous traits and by pairwise concordance for dichotomous traits. The relationship between age of onset and APOE genotype was examined using linear regression analysis. RESULTS: Significant familial effects on age of onset (intraclass correlation 0.41) and mood state (intraclass correlation 0.26), and a relatively high pairwise concordance for agitation (excess concordance 0.1) were found. The APOE locus was found to account for 4% of the variance in age of onset. CONCLUSIONS: Substantial familial influence on age of onset, depression and agitation suggests that genotype does influence phenotype in Alzheimer's disease. Establishing the molecular basis for this phenotypic variation may prove relevant to other neuropsychiatric disorders.

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 > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Royal College of Psychiatrists
ISSN: 0007-1250
Last Modified: 24 Dec 2017 21:12

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