Novel genes have been identified as possible contributors to bipolar disorder. The condition, also known as manic-depressive illness, is a chronic and devastating psychiatric illness, affecting 0.5-1.6% of the general population across their lifetime. Its causes are not yet fully understood, but genetic factors are thought to play a large role.

Professor Markus Nothen of the University of Bonn, Germany, explains, “There is no one gene that has a significant effect on the development of bipolar disorder. Many different genes are evidently involved and these genes work together with environmental factors in a complex way.”

His international team analyzed genetic information from 2,266 patients with bipolar disorder and 5,028 comparable people without bipolar disorder. They merged these individuals’ information with that of thousands of others held in previous databases. Altogether, this included the genetic material of 9,747 patients and 14,278 non-patients. The researchers analyzed about 2.3 million different regions of DNA.

This highlighted five areas that appeared to be connected to bipolar disorder. Two of these were new gene regions containing “candidate genes” connected to bipolar disorder, specifically the gene “ADCY2” on chromosome five and the so-called “MIR2113-POU3F2” region on chromosome six.

The remaining three risk regions, “ANK3”, “ODZ4” and “TRANK1”, were confirmed to be linked to bipolar disorder, having been previously suspected to play a role. “These gene regions were statistically better confirmed in our current investigation, the connection with bipolar disorder has now become even clearer,” said Professor Nothen.

Full details appear in the journal Nature Communications. The authors write, “Our finding provides new insights into the biological mechanisms involved in the development of bipolar disorder.”

“The investigation of the genetic foundations of bipolar disorder on this scale is unique worldwide to date,” says study co-author Professor Marcella Rietschel. “The contributions of individual genes are so minor that they normally cannot be identified in the ‘background noise’ of genetic differences. Only when the DNA from very large numbers of patients with bipolar disorder are compared to the genetic material from an equally large number of healthy persons can differences be confirmed statistically. Such suspect regions which indicate a disease are known by scientists as candidate genes.”

One of the newly discovered gene regions, “ADCY2”, was of particular interest to Professor Nothen. This section of DNA oversees the production of an enzyme used in the conduction of signals into nerve cells. He said, “This fits very well with observations that the signal transfer in certain regions of the brain is impaired in patients with bipolar disorder. Only when we know the biological foundations of this disease can be also identify starting points for new therapies.”