CAG REPEAT EXPANSIONS AND SCHIZOPHRENIA - ASSOCIATION WITH DISEASE INFEMALES AND WITH EARLY AGE-AT-ONSET

An increase in the severity of schizophrenia through consecutive gener ations (anticipation) has been found in some studies of families with affected members. Anticipation in five neurological disorders is known to arise from the expansion of CAG repeats between generations of aff ected individuals. The 'repeat expansion detection' method was used to screen individual genomes for the size of such expansions in a sample of schizophrenic and normal subjects. Comparison of the frequency dis tribution of CAG expansions observed in schizophrenic patients to that for normal subjects, showed that there are significantly more expansi ons in patients (p = 0.048). When male and female subjects are conside red separately, there is a highly significant difference in the distri bution of repeat sizes found between affected and normal females (p = 0.0023) but no significant difference between affected and normal male s. Overall there is a 28% excess of expansions observed in affected ve rsus normal females, and their presence confers a relative risk of 4.1 2 (p < 0.005). In contrast, the frequency distribution of age-at-onset with respect to repeat size is nearly the same in male and female pat ients and, when the sexes are combined, the larger (CAG)(69-136) expan sions are associated with a younger age-at-onset (p = 0.02).