Sorting through the genetics of bipolar disorder

Genetic factors play a role in bipolar disorder, but defining those factors has proven an arduous task. At least sixteen different linkages on eleven different chromosomes are claimed in the scientific literature. The literature also includes many subsequent studies casting doubt on these claims. Yet all these studies do provide something of great value: the raw genotypic data that was gathered in each. By combining all of these raw data into the largest meta-analysis of any psychiatric disorder to date, an international group of scientists have now established significant linkage of bipolar disorder to two chromosomal sites. This paves the way for gene discovery and, in time, valid targets for potential new therapeutic approaches. The study appears in the October 2005 issue of the American Journal of Human Genetics.

Two particular chromosomal regions stand out in this study: 6q and 8q. Some previous studies have implicated 6q, but 8q is a novel finding. Although there are still a lot of genes in these regions, there are far fewer to sort through than if all the suggested linkages in the literature were pursued. Pamela Sklar, an associate member of the Broad Institute of MIT and Harvard and an assistant professor of psychiatry at Massachusetts General Hospital (MGH), will lead a group of researchers from Broad, MGH, the Harvard School of Public Health and the University of Pittsburgh to dissect these regions to determine the genes involved.

There have been previous meta-analyses performed, but always with the summaries of data from individual analyses. In this study, the scientists were able to collate raw genotype data from over 5000 individuals (1067 families), which also has the advantage of controlling for variability in the original studies. This approach reflects the growing availability of genome-scan data, and suggests that diseases, that have multiple genetic components such as bipolar disorder, will also be amenable to this kind of study.

Bipolar disorder is undoubtedly more complicated at the genetic level than just two loci. Yet the strong linkages found by this scientific collaboration give researchers worldwide a solid starting place from which to tease out bipolar's genetic secrets, and use those secrets against it.

Paper(s) cited

McQueen, et al. Combined Analysis from Eleven Linkage Studies of Bipolar Disorder
Provides Strong Evidence of Susceptibility Loci on Chromosomes 6q and
. The American Journal of Human Genetics, Volume 77, Issue 4, Pages 582-595. DOI:10.1086/491603