Genetics of bipolar disorder.

Family and twin studies have consistently documented that bipolar disorder (BPD) is familial and heritable, but efforts to identify specific susceptibility genes have been complicated by the disorder's genetic and phenotypic complexity. Genetic linkage studies have implicated numerous chromosomal regions, but findings have been inconsistent. As with other complex disorders, it has become clear that linkage analysis lacks the power and precision to identify susceptibility loci for BPD. Candidate gene association studies have implicated several specific genes, but these studies have been limited by our incomplete understanding of the disorder's biology, and there have been few robustly replicated results. Within the past 2 years, a major advance in the genetics of complex disease has become feasible in the form of genome-wide association studies. Such studies, which require large sample sizes, have already proven successful in identifying susceptibility variants for a range of common medical disorders. Genome-wide association studies have begun to appear for BPD, and more are in progress. By providing an unbiased approach, this technology may reveal novel biological mechanisms underlying BPD.