Bipolar disorder (BPD) and schizophrenia (SZ) are common, sever psychiatric syndromes which are partially heritable. Five linkage studies have identified 18p11.2 as a candidate region, which contains a susceptibility gene for BPD and/or SZ. One of the groups reporting linkage also reports strong (p=0.00009) linkage disequilibrium (LD) between SZ and an 18p11.2 (CA)n repeat polymorphism, located in intron 5 of a G-protein subunit gene, GOLF. We have discovered a novel 18p11.2 candidate susceptibility gene in GOLF intron 5. This novel gene, which contains the GOLF (CA)n repeat in its 3'TTR, encodes a brain-specific secreted neuropeptide. This novel gene has no homology to any gene n the public databases. It is an intronless gene with a 116 amino acid open reading frame, including a signal peptide. In situ hybridization and immunohistochemistry reveal that expression is limited to the hippocampus, amygdala and entorhinal cortex. No peripheral expression has been detected. A case-control association study of transcribed variants yields evidence for association with SZ. These data suggest that this novel candidate gene deserves further study. Support is requested for family-based LD studies of these (and other) variants in both BPD and SZ. We have assembled sets (n>600) of parent-child trios for both SZ and BPD to test the hypothesis that variation in this gene increases risks for these disorders. These studies may identify a susceptibility gene for SZ and/or BPD.
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