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Bipolar Disorder: Expanded Search for Genes Finds Clues
Edward R. Winstead

Using the largest collection of families ever assembled for a genetic study of bipolar disorder, researchers have identified two regions of the human genome that may contain susceptibility genes for the disease. While no genes have yet been found, the researchers are confident that by studying hundreds of families, they will eventually pinpoint genes involved in the disease.

“I’m optimistic, and I think we’ve turned a corner,” says John I. Nurnberger Jr. of Indiana University in Indianapolis, who coordinated the study. “We now realize the necessity of studying large samples of patients.”

Graphs representing the presence of possible susceptibility genes on chromosomes 6 and 17 but not on chromosome 1. The x-axis shows the LOD score; the y-axis shows the distance along the chromosome.

The research is part of an ongoing study of bipolar disorder in nearly 700 families and is funded by the National Institute of Mental Health in Bethesda, Maryland. Recognizing the need to recruit more families for the research, the study expanded in 1998 to 10 medical centers from 4.

No genes have been definitively linked to bipolar disorder, which involves debilitating extremes in mood and is also known as manic depression.

Like other complex disorders, such as diabetes and heart disease, bipolar disorder probably involves many susceptibility genes as well as environmental risk factors. Different genes may be important in different families, perhaps even in the same family.

“A single gene may have a strong effect in one family and not another,” Nurnberger says.

In the study, the researchers “scanned” the genomes of more than a thousand individuals from 250 families—each of which had at least two affected members—to identify regions of DNA shared by people with the disorder.

The data indicate that potential susceptibility genes reside on chromosomes 6 and 17. These regions have not been prominent in most other studies of bipolar disorder, but the results are consistent with the notion that the disease involves multiple genes. Researchers are scrutinizing the two regions for possible susceptibility genes.

The collaborative project aims over a period of years to identify multiple susceptibility genes and to look for common biochemical mechanisms that may influence the onset of bipolar disorder. Success in this work might allow the development of new medications and treatment strategies.

Many of the drugs used today to treat the disorder, such as lithium, were found serendipitously.

“There has been little empirical data to guide the development of pharmaceuticals,” says Nurnberger.

The other institutions participating in the study were the University of California, Irvine; the University of California, San Diego; the University of Pennsylvania; the University of Iowa; the University of Chicago; Rush-Presbyterian Medical Center, Chicago; Washington University, St. Louis; the University of Louisville; Wayne State University, Detroit; Johns Hopkins University, Baltimore; and the National Institutes of Mental Health Intramural Research Program, Bethesda, Maryland.

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Dick, D.M. et al. Genomewide linkage analyses of bipolar disorder: A new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative. Published online in the American Journal of Human Genetics (May 27, 2003).

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