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© 1995 Oxford University Press

OTHER

CAG repeat expansions and schizophrenia: association with disease in females and with early age-at-onset

A.G. Morris, E. Gaitonde1, P.J. McKenna2, J.D. Mollon1 and D.M. Hunt*

Department of Molecular Genetics, Institute of Ophthalmology, University College London Bath St., London 1Department of Experimental Psychology University of Cambridge, Cambridge 2Fulbourn Hospital Cambridge, UK

*To whom correspondence should be addressed

Received July 25, 1995; Revised August 9, 1995; Accepted August 9, 1995

An increase in the severity of schizophrenia through consecutive generations (anticipation) has been found in some studies of families with affected members. Anticipation in five neurologlcai disorders is known to arise from the expansion of CAG repeats between generations of affected individuais. The ‘repeat expansion detection’ method was used to screen indlviduai genomes for the size of such expansions in a sampie of schizophrenic and normai sub jects. Comparison of the frequency distribution of CAG expansions observed in schizophrenic patients to that for normal subjects, showed that there are significantly more expansions in patients (p = 0.048). When male and female subjects are considered separateiy, there is a highly significant difference in the distribution of repeat sizes found between affected and normal females (p = 0.0023) but no significant difference between affected and normal males. Over all there is a 28% excess of expansions observed in affected versus normal females, and their presence confers a relative risk of 4.12 (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 patients and, when the sexes are combined, the larger (CAG)69–136 expansions are associated with a younger age-at-onset (p = 0.02).


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