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Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population.

Payton, A. and Holland, F. and Diggle, Peter J. and Rabbitt, P. and Horan, M. and Davidson, Y. and Gibbons, L. and Worthington, J. and Ollier, W. E. R. and Pendleton, N. (2003) Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population. Molecular Psychiatry, 8. pp. 14-18. ISSN 1359-4184

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Abstract

General intelligence is a heritable trait that is a risk factor for both the onset of dementia and the rate of cognitive decline in community-dwelling older persons. Previous studies screening for quantitative trait loci (QTLs) that influence general intelligence in healthy individuals have identified four loci, two of which are located within the genes insulin-like growth factor 2 receptor (IGF2R) and the Msx1 homeobox. Here, we report the finding of another QTL associated with general intelligence that is located within exon 2 of the cathepsin D (CTSD) gene. A group of 767 healthy adults with a follow-up period of over 15 years have been analyzed for cross-sectional and longitudinal trends in cognitive change using the Heim intelligence test score (AH4-1). We observed a significant association (P=0.01) between a functional C>T (Ala>Val) transition within exon 2 of the CTSD gene that increases the secretion of pro-CTSD from the cell, and the AH4-1 score at initial testing on entry to the longitudinal study. Interestingly, CTSD is transported by IGF2R from the trans Golgi network to the lysosome.

Item Type: Article
Journal or Publication Title: Molecular Psychiatry
Uncontrolled Keywords: cathepsin D ; intelligence ; cognitive decline ; polymorphism ; association
Subjects: R Medicine > R Medicine (General)
Departments: Faculty of Health and Medicine > Medicine
VC's Office
ID Code: 10006
Deposited By: Mrs Yaling Zhang
Deposited On: 25 Jun 2008 16:42
Refereed?: Yes
Published?: Published
Last Modified: 26 Jul 2012 14:41
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/10006

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