A Payton (1), F Holland (2), P Diggle (3), P Rabbitt (4), M Horan (5), Y Davidson (5), L Gibbons (5), J Worthington (1), W E R Ollier (1) and N Pendleton (5)

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

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

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

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

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

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, the authors 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). The authors 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
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Contact: Aimee Midei
molecularpsychiatry@mednet.ucla.edu
310-206-6739
Molecular Psychiatry
13-Feb-2003