Manic depression linked to two chromosomal regions in the human genome

An international team of 53 researchers has offered the most convincing evidence so far linking bipolar disorder, also known as manic depression, to two chromosomal regions in the human genome. The finding gives scientists refined targets for further gene studies.

"Even though bipolar disorder affects millions of people around the world--sometimes throughout their lifetimes--what we understand to be biologically relevant at the genetic level is not terribly characterized," said Matthew McQueen, lead author and postdoctoral fellow in the Department of Epidemiology at the Harvard School of Public Health (HSPH). "This research can help focus the field to identify viable candidate genes."

The study will appear in the October issue of the American Journal of Human Genetics and is available now in the journal's electronic edition online.

More than two million American adults have bipolar disorder, according to the National Institute of Mental Health. Patients typically experience dramatic mood swings from episodes of euphoria and high energy to feelings of intense sadness, fatigue, and even suicide. Psychiatrists have identified two primary forms of the illness: bipolar I disorder, which is the classic form of recurring mania and depression, and bipolar II disorder, which has less severe episodes of mania. Treatment often includes medication.

The exact cause of the illness remains unknown, but scientists suspect the involvement of several genes, coupled with environmental influences. A number of individual studies have suggested genomic regions linked to bipolar disorder, but their results have been inconsistent and difficult to replicate, leaving the field "standing at a crossroads, wondering in which direction to go next," said McQueen.

To establish more definitive research, McQueen and his colleagues did something unusual. They secured and then combined original genome scan data from 11 independent linkage studies, instead of relying on the more common approach of using summary data from such studies.

"The use of original data made a significant difference in our ability to control for variation in several factors among the different data sets and to make the overall analysis much more consistent and powerful," said Nan Laird, HSPH Professor of Biostatistics and senior author on the paper.

The resulting analysis involved 1,067 families and 5,179 individuals from North America, Italy, Germany, Portugal, the UK, Ireland, and Israel, who had provided blood samples and family medical histories. The research team combined the data into a single genome scan and found strong genetic signals on chromosomes 6 and 8. The team now hopes to narrow the search to find associations between specific genes and the mental illness.

The analysis was funded through the Study of Genetic Determinants of Bipolar Disorder Project at the National Institute of Mental Health. Other researchers on the analysis team represented Massachusetts General Hospital, The Broad Institute, and the University of Pittsburgh.

http://www.hsph.harvard.edu/