Identification, characterization, and association analysis of novel genes from the bipolar disorder susceptibility locus on chromosome 4q35.

The cause of bipolar disorder remains unknown, with little knowledge of the underlying biological, anatomical, biochemical, or genetic defect. The disorder is genetically complex, with an increasing number of loci being implicated through genetic linkage studies. We previously identified a bipolar disorder susceptibility locus on chromosome 4q35 and refined the interval harboring this susceptibility gene to approximately 5 Mb, a size that is amenable to positional cloning. Several independent studies have reported the presence of a susceptibility gene at this locus. To identify candidate genes for testing for association with bipolar disorder, we previously established a transcript map that encompasses the candidate interval. We have continued to seek novel genes from this region in order to expand this transcript map. Here, we describe the further identification and characterization of eight novel genes from the chromosome 4q35 bipolar candidate interval. Expression analysis determined that six of these novel genes are expressed in the brain, and these genes were therefore analyzed for association with bipolar disorder. Single nucleotide polymorphisms were identified from the candidate genes and tested for association in our case-control cohort. Our data suggest that the six candidate genes analyzed can be excluded from involvement in the disorder.