Mutational analysis of phospholipase A2A: a positional candidate susceptibility gene for bipolar disorder

Abstract

Evidence for the involvement of genetic factors in the pathogenesis of bipolar affective disorder is now well established.¹ However, the mode of inheritance is non-mendelian and this makes the identification of susceptibility loci difficult. A short-cut to localisation of a disease gene for an oligogenic/multifactorial disorder such as bipolar disorder may come from observation of cosegregation with a monogenic trait. We have described a family (pedigree 324) in which there was cosegregation of major affective disorder and Darier's disease, a dominantly inherited skin disorder, and hypothesised that this reflects genetic linkage between genes involved in these disorders.² Genetic mapping studies have placed the locus for Darier's disease on chromosome 12q23–q24.^3–7 We conducted subsequent linkage studies (1995) upon 45 bipolar families (without Darier's disease). These results showed some evidence in favour of linkage with chromosome 12q markers with maximum evidence at a trinucleotide repeat marker within intron 1 of the phospholipase A2A (PLA2A) gene.⁸ Evidence for linkage was more significant when analysing the 22 families comprising the Cardiff centre sample, which were expected to be most genetically similar to pedigree 324.