Project Summary

Wade Berrettini, M.D., Ph.D. (Distinguished Investigator 2004) of University of Pennsylvania, notes that recent epidemiological, genetic linkage and molecular data suggest an overlap in inherited vulnerability for bipolar disorder (BPD) and schizophrenia (SZ). Dr. Berrettini replicated results from another study which found that in addition to 18p11.2 linkage, there is linkage disequilibrium (LD) to a (CA)n repeat polymorphism found in intron 5 of the Golf gene. This allele was transmitted 45 out of 58 times from heterozygous parents to affected offspring. He then found, in a search for novel genes near this site, evidence that Golf intron 5 contains approximately 4 genes. Further, a metallophosphoesterase gene (MPPE1), oriented in the opposite direction, shares 3’UTR sequence with Golf. Preliminary genotyping in BPD cases and controls yielded LD with BPD for the C18orf2 gene. Given the proximity of these genes to the (CA)n repeat polymorphism in Golf, he will now search for BPD and SZ susceptibility sequences in the region, using DNA samples from BPD and SZ patients participating in the NIMH Genetic Initiative. Nearly all individuals in the sample are of European origin, and include approximately 700 unrelated individuals with familial BPD and approximately 600 unrelated individuals with familial SZ and approximately 600 controls who have been screened for psychiatric disorders. Dr. Berrettini will now conduct dense SNP genotyping across the Golf gene region, extending in either direction from the (CA)n. In summary, Dr. Berrettini will use genetic linkage analysis in a large group of patients with either familial BPD or SZ to identify candidate genes that underlie vulnerability to these diseases.

Program Area: MULTIPLE FOCUS AREAS\Bipolar Disorder/Schizophrenia

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