No evidence of association from transmission disequilibrium analysis of the hKCa3 gene in bipolar disorder

Objective: A recent case-control study has suggested that modest enlargemen ts of a highly polymorphic CAG repeat in exon 1 of the gene encoding potass ium channel hKCa3 may be associated with bipolar disorder (BPD). We have ex amined this hypothesis by genotyping this locus in a family-based associati on study. Method. One hundred and twenty-eight parent-offspring trios of British Cauc asian origin were examined where the proband was diagnosed with the America n Psychiatric Association's Diagnostic and Statistical Manual (DSM)-IV BPD I (n - 123) or II (n = 5). An improved assay was used, with redesigned poly merase chain reaction (PCR) primers. permitting quicker and higher resoluti on genotyping. The resultant genotypes a ere analysed using the extended tr ansmission/disequilibrium test (ETDT). Results: The experimental data did not provide evidence for the preferentia l transmission of large alleles to bipolar cases (chi (2) = 11.12, df = 10, p = 0.349). Conclusions: Our data provide no support for the hypothesis that variation at the hKCa3 ene contributes to susceptibility: to BPD.