RESUMO
OBJECTIVE: Linkage and association studies of bipolar affective disorder (BAD) point out chromosome 12q24 as a region of interest. METHODS: To investigate this region further, we conducted an association study of 22 DNA markers within a 1.14 Mb region in a Danish sample of 166 patients with BAD and 311 control individuals. Two-hundred and four Danish patients with schizophrenia were also included in the study. RESULTS: We observed highly significant allelic and genotypic association between BAD and two highly correlated markers. The risk allele of both markers considered separately conferred an odds ratio of 2 to an individual carrying one risk allele and an odds ratio of 4 for individuals carrying both risk alleles assuming an additive genetic model. These findings were supported by the haplotype analysis. In addition, we obtained a replication of four markers associated with BAD in an earlier UK study. The most significantly associated marker was also analyzed in a Scottish case-control sample and was earlier associated with BAD in the UK cohort. The association of that particular marker was strongly associated with BAD in a meta-analysis of the Danish, Scottish and UK sample (P=0.0003). The chromosome region confined by our most distant markers is gene-poor and harbours only a few predicted genes. This study implicates the Slynar locus. We confirmed one annotated Slynar transcript and identified a novel transcript in human brain cDNA. CONCLUSION: This study confirms 12q24.3 as a region of functional importance in the pathogenesis of BAD and highlights the importance of focused genotyping.