A linkage study of families positive for bipolar disorder and a high rate of attempted suicides strongly suggests that one or more genes in a specific region of chromosome 2 are associated with increased risk for attempted suicide, according to an article in the March issue of Biological Psychiatry.

The Johns Hopkins-led study identified a particular area of the genome on chromosome 2 that has been implicated in two additional recent studies of attempted suicide. An estimated 4.6 percent of Americans ages 15 to 54 years have tried to commit suicide, according to the authors.

“We’re hoping our findings will eventually lead to tests that can identify those at high risk for attempting suicide,” says Virginia Willour, PhD, an assistant professor in the Department of Psychiatry at the Johns Hopkins University School of Medicine and lead author of the study.

The investigators conducted a family linkage study in which they searched for commonalities in the genomes of family members with bipolar disorder and a history of attempted suicide. The same gene region on chromosome 2 that was identified by this bipolar disorder and attempted suicide study was recently identified by two complementary family studies that looked at attempted suicide in families with major depression and alcohol dependence.

“Family linkage studies are not always consistent, so the fact that all three studies, including ours, point to the same region of the genome is a good indication that we are on the right track toward identifying a gene or genes that play a role in why a person chooses to take his or her own life,” said Willour.

In the multi-institutional study, researchers examined data from 162 families with bipolar disorder. They looked at attempted suicide in this sample because it is an important clinical problem that tends to occur more often in some of these families than in others, suggesting a distinctive genetic basis, said senior author James B. Potash, MD, MPH, of the Department of Psychiatry at Hopkins. This technique, of looking at sub-types of illness, is used by genetic researchers as a way to reduce genetic complexity.

From the 162 families, the researchers selected 417 subjects who were diagnosed with schizoaffective/bipolar disorder or bipolar I or II disorder.

These subjects were asked whether they had ever attempted suicide and the degree of intent of the most serious attempt. Of the total, 154 subjects said they had attempted suicide, and 122 stated that they had “definite” intent. For the purpose of this study, the latter were considered to have a history of attempted suicide.

Data for all 417 subjects was entered into a computer program that looks for genetic similarities between subjects with similar psychological profiles. Results indicated that family members with a history of attempted suicide and bipolar disorder showed a high degree of genetic similarity at a specific area -- DNA marker D2S1777 -- on a section of chromosome 2 referred to as 2p12.

The same marker was implicated in a 2004 study from the University of Pittsburgh School of Medicine that looked at attempted suicide and major depression. It is close to another marker, D2S1790, located in the 2p11 region of chromosome 2, which was identified in a 2004 study from the University of Connecticut School of Medicine that looked at alcoholism and attempted suicide.

Willour said that although the Hopkins-led study does not pinpoint a specific gene responsible for attempted suicide, it does suggest a “neighborhood” in which the gene might be found. She adds that the next step is to further narrow the search and find the “address.” “Once we have located the specific gene,” she says, “we can better identify people who might be at risk of suicide and offer drug companies a target for possible therapies.”