Research — 09 May 2016

Bipolar disorder, previously called manic depression, causes dramatic shifts in mood, along with swings in activity and energy levels.

Thought to affect almost 1 to 3 percent of Americans, bipolar disorder can be an incredibly disruptive condition.

Bipolar disorder is thought to share a common genetic origin with a number of other psychiatric conditions. Although evidence of this connection is growing, the search is still in its infancy.

New research, led by Dr. James Potash, puts another gene-shaped piece in the jigsaw. The study was a joint venture, conducted at the University of Iowa Carver College of Medicine, Johns Hopkins School of Medicine in Baltimore, MD, and Cold Spring Harbor Laboratory, NY.

Bipolar disorder is known to run in families, and previous research seems to point to a genetic component.

These earlier studies uncovered a number of common variations that occur more often in people with bipolar disorder. However, these common variations only seem to have a minimal effect on psychiatric outcomes.

A new phase of genetic discovery

The most recent genetic studies, using more powerful sequencing technology, have also identified rarer variations that, individually, might have a more significant impact than the common variations. It is these rarer components that were the focus of this latest research.

Until now, rarer genetic variations have been relatively unstudied due to the cost implications, but, leaps forward in technology have made the procedures much more accessible.

“Common variations are thought to, each individually, have only a tiny impact – for example, increasing a person’s likelihood of getting a disease by 10 to 20 percent. The hope with rare variations is that they, individually, have a much bigger impact, like doubling or quadrupling risk for disease.” Prof. James Potash M.D.

Dr. Potash and his team designed a two-pronged approach to their study. First, they used a case-control approach.

In a nutshell, this type of approach compares the genomes of people carrying a certain condition with individuals without the condition. The data is then screened to find any particular sequences that appear more frequently in one group than the other.

The second phase of the trial used so-called family-based exome sequencing. This procedure involves examining the genomes of individuals with bipolar disorder and their family members. Exome sequencing helps researchers see which genes “travel with” bipolar disorder or segregate with the condition.

New bipolar genes revealed

During the exome sequencing, the team found 84 rare variants that segregated with bipolar disorder. These variants were also predicted to damage the protein that the gene was responsible for coding.

Next, the team took these 84 variants and tested them in a larger sample of bipolar individuals using a case-control approach; in this stage, the researchers delved into the genome of 3,541 individuals with bipolar disorder and 4,774 controls.

In the second phase of the experiment, the researchers could not definitively link any of the variants to bipolar disease. However, they did discover that 19 genes were more common in bipolar disease genomes than the controls.

“The results were not strong enough for us to say ‘we have pinpointed the genetic culprits.’ But it was strong enough for us to remain interested in these genes as potential contributors to bipolar disorder.”Prof. James Potash M.D.

 

An intriguing twist came at the tail end of the study when the team collated the 84 gene variants; they noticed that many of them had previously been linked to schizophrenia and autism.

When the team then looked in detail at the 19 rare genes, Dr. Potash found that “the autism genes continued to be unexpectedly prominent among them.”

Although the results of the research are not as clear and decisive as the team hoped, they do add another layer of evidence to the pot.

The researchers hope that these genetic clues will prompt further investigation. In the long run, the findings will help propel the medical world toward new treatments for the millions of individuals affected by bipolar disorder and other psychiatric conditions.

This article first appeared on ‘Medical News Today’ on 6 May 2016.

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