title: Cathepsin D exon 2 polymorphism associated with general intelligence in a healthy older population.
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.
authors.affiliation: Centre for Integrated Genomic Medical Research, Manchester University, UK. tony@s1.ser.man.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Payton
authors.forename: F
authors.initials: F
authors.lastname: Holland
authors.forename: P
authors.initials: P
authors.lastname: Diggle
authors.forename: P
authors.initials: P
authors.lastname: Rabbitt
authors.forename: M
authors.initials: M
authors.lastname: Horan
authors.forename: Y
authors.initials: Y
authors.lastname: Davidson
authors.forename: L
authors.initials: L
authors.lastname: Gibbons
authors.forename: J
authors.initials: J
authors.lastname: Worthington
authors.forename: W E R
authors.initials: WE
authors.lastname: Ollier
authors.forename: N
authors.initials: N
authors.lastname: Pendleton
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002402:Cathepsin D / Q000235:genetics*; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D002402:Cathepsin D