No evidence of linkage disequilibrium between a CAG repeat in the SCA1 gene and schizophrenia in Caucasian and Chinese schizophrenic subjects

Abstract

Several recent studies have reported evidence for a schizophrenia locus on chromosome 6p, with a variety of linked markers spanning a ~ 40 cM region between D6S470 and D6S291. However because of the wide region implicated and the difficulty of inferring phenotype from genotype in complex disorders, it is difficult to define its location precisely using linkage data. An alternative approach is to search for linkage disequilibrium. On chromosome 6p, allelic association with a (CAG) 29 allele of a triplet repeat marker in the SCA1 gene has been reported, and we have attempted to replicate this finding using a Caucasian case-control sample of 211 affected subjects and 204 controls, and a Han Chinese sample of 100 affected family trios. In the case-control sample, the frequency of the (CAG) 29 allele was similar in cases and controls (35), and no other alleles provided evidence for allelic association. Likewise, there was no evidence for preferential transmission of the (CAG) 29 allele to affected offspring in the Chinese sample, although a different allele, (CAG) 26, was more often transmitted to the affected offspring. However this data did not reach statistical significance (P = 0.1). We conclude that our data does not support the notion that there is a locus for schizophrenia close to the SCA1 gene. However, since linkage disequilibrium will vary between distinct populations, we cannot exclude this possibility. (C) 1999 Lippincott Williams and Wilkins.