A success at the end of an era, and a glimpse of things to come.

摘要

In the field of bipolar disorder genetics, the linkage era will not be widely mourned. The many linkage studies conducted over a period of more than 20 years have not produced signals that are robust and localized enough to allow the efficient identification of risk alleles. Even when risk alleles have been successfully identified within linkage regions, such as in the region on chromosome 13 harboring the gene DAOA (2), the alleles have not been consistently replicated across samples (3). Still, many of the linkage findings to date will probably prove to harbor one or more genes involved in bipolar disorder susceptibility. The problem is one of sorting the wheat from the chaff. Genome-wide association studies may provide some answers in the near future by revealing which of the linkage regions actually contain susceptibility genes. In this way, the modest findings of the linkage era can still inform our choices as we prioritize the many signals that will likely emerge from genome-wide association results.