¹Division of Molecular Neurobiology, Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany

Correspondence: D Rujescu, MD, Division of Molecular Neurobiology, Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstr. 7, D-80336 Munich, Germany. E-mail: Dan.Rujescu@psy.med.uni-muenchen.de

Received 19 November 2002; Revised 23 December 2002; Accepted 10 January 2003.

Abstract

Correlations between general intelligence (g) and brain volume are about 0.40, and the correlation between g and white matter volume has been reported to be largely due to genetic factors. Establishing that the correlation between brain volumes and cognitive abilities is mediated by shared genetic factors is only the first step in unveiling the relation between them. We have recently shown that methionine at codon 129 in the prion protein is associated with white matter reduction in a group of healthy volunteers and schizophrenic patients. The present study examines the influence of the same genetic variation on psychometric cognitive performance measurements in 335 community-based healthy volunteers. The polymorphism was associated with Full Scale IQ (genotype: F=4.38, df=2/317, P=0.013; allele: F=8.04, df=1/658, P=0.005), as measured by HAWIE-R (German version of the Wechsler Adult Intelligence Scale, Revised). Genotype accounted for 2.7% of the total variability in Full Scale IQ (partial ²=0.027). An exploratory analysis revealed association with several HAWIE-R subscales; the association with the Digit Symbol subtest remained significant after correction for multiple testing. In summary, we deliver evidence for an association of a common genetic variation in the prion protein gene with cognitive performance. However, independent replications are needed before firm conclusions can be drawn.