Association study of bipolar disorder at the phospholipase A2 gene (PLA2A) in the Darier's disease (DAR) region of chromosome 12q23-q24.1

We have previously described a pedigree in which affective disorder and Darier's disease cosegregate and, in an independent sample of 45 bipolar pedigrees, reported evidence in support of linkage between a putative susceptibility locus for bipolar disorder and markers in the Darier's disease region of chromosome 12q23-q24.1. The maximum evidence for linkage was given by a polymorphism at the gene encoding secretory phospholipase A2 (PLA2A), a candidate gene for affective disorder. Dawson et al. (Psychiatric Genetics, 5, 177-180) recently reported allelic association with the same polymorphism at PLA2A in a sample of 54 bipolar probands and 56 controls. We have been unable to replicate the association in 127 Caucasian British DSMIII-R bipolar probands and 223 Caucasian British controls. However, on the basis of several lines of evidence discussed in the paper, we believe that this genomic region in general, and the PLA2A gene in particular, are worthy of further study as candidates in the search for susceptibility genes for the functional psychoses.