Possible parent-of-origin effect of dopa decarboxylase in susceptibility to bipolar affective disorder

Dopa decarboxylase (DDC) catalyses the synthesis of both dopamine and serotonin as well as trace amines suggested to possess neuromodulating capabilities. We have previously reported evidence suggesting an association between DDC and bipolar affective disorder (BPAD) [Borglum et al., 1999]. To further investigate the possible role of DDC in BPAD, we analyzed a 1- and a 4-bp deletion variant-both of putative functional significance in two new samples: a case-control sample with 140 cases and 204 controls, and 100 case-parents trios. We also tested for association in subjects with familial disease in both the new and the previously investigated samples. The previously reported association was not replicated in either of the new samples. However, a preponderance of the 1-bp deletion was increased by analysis of the familial cases separately for all case-control samples investigated, indicating a possible association with familial disease (combined analysis, P=0.02). In the trio sample, a preferential paternal transmission of the 4-bp deletion was observed (P=0.006). DDC is located next to the imprinted gene GRB10, which is expressed specifically from the paternal allele in fetal brains. Increased transmission of paternal DDC alleles has also been suggested in attention deficit hyperactivity disorder. We suggest that DDC might confer susceptibility to BPAD predominantly when paternally transmitted. (C) 2003 Wiley-Liss, Inc.