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Review Article

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

Molecular Psychiatry volume 8, pages 14–18 (2003)Cite this article

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.

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Acknowledgements

This work was supported by the Wellcome Trust. Blood collection and DNA extraction was funded by Research into Ageing.

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Authors and Affiliations

  1. Centre for Integrated Genomic Medical Research, Stopford Building, Manchester University, Oxford Road, Manchester, M13 9PT, UK

    A Payton, J Worthington & W E R Ollier

  2. GlaxoSmithKline, NFSP (S), Third Avenue, Harlow, CM19 5AW, UK

    F Holland

  3. Department of Mathematics & Statistics, Medical Statistics Unit, University of Lancaster, Lancaster, LA1 4YF, UK

    P Diggle

  4. Age & Cognitive Performance Research Centre, University of Manchester, Zochonis Building, Oxford Road, Manchester, M13 9PL, UK

    P Rabbitt

  5. Clinical Gerontology, University of Manchester, Clinical Sciences Building, Hope Hospital, Stott Lane, Salford, Greater Manchester, M6 8HD, UK

    M Horan, Y Davidson, L Gibbons & N Pendleton

Authors
  1. A Payton
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  2. F Holland
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  3. P Diggle
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  4. P Rabbitt
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  7. L Gibbons
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  8. J Worthington
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  9. W E R Ollier
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  10. N Pendleton
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Correspondence to A Payton.

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Payton, A., Holland, F., Diggle, P. et al. Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population. Mol Psychiatry 8, 14–18 (2003). https://doi.org/10.1038/sj.mp.4001239

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  • DOI: https://doi.org/10.1038/sj.mp.4001239

Keywords

  • cathepsin D
  • intelligence
  • cognitive decline
  • polymorphism
  • association

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