ANALYSIS OF THE CAG REPEATS IN THE SCA1 AND B37 GENES IN SCHIZOPHRENIC AND BIPOLAR-I DISORDER PATIENTS - TENTATIVE ASSOCIATION BETWEEN B37 AND SCHIZOPHRENIA

We have genotyped unrelated French Alsatian schizophrenic and bipolar I disorder (BPD) patients and matched controls for the polymorphic GAG ; repeats within the genes for spinocerebellar ataxia type 1 (SCA1) an d dentatorubral-pallidoluysian atrophy (B37), in order to test their p ossible involvement in these disorders. No alleles with abnormally exp anded repeats were found in either gene in patients and controls. Diff erences in allele and genotype frequencies for the SCA1 CAG repeat bet ween patients and controls were not significant, thus providing no sup port for its role as a possible positional candidate gene for schizoph renia and BPD in our patients. Chi square testing revealed a significa nt result (P = 0.019) for an association between the B37 CAG repeat on chromosome 12p and schizophrenia, This result was more significant wh en only schizophrenics with a positive family history were compared wi th controls (P = 0.0001), The frequencies of alleles with 14, 12, and 15 GAG; repeats differed the most, respectively, between schizophrenic s and controls, When choosing the median of the B37 allele distributio n (15 CAG repeats) as a threshold, there were significantly more contr ols than schizophrenics in the group with longer alleles (15 or more r epeats) and more schizophrenics with shorter alleles (P = 0.002 by Fis her exact test). No particular genotype was associated with schizophre nia, This result possibly indicates linkage disequilibrium with anothe r locus on chromosome 12p and therefore deserves further attention. No association was found between the B37 CAG repeat and patients with BP D, Am. J. Med. Genet. 74:324-330, 1997. (C) 1997 Wiley-Liss, Inc.