Bipolar risk boosted by accumulation of rare versions of genes

A buildup of rare versions of genes that control the activity of nerve cells in the brain increases a person’s risk for bipolar disorder, researchers suggest in a paper posted online the week of February 16 in Proceedings of the National Academy of Sciences.  

“There are many different variants in many different genes that contribute to the genetic risk,” says coauthor Jared Roach, a geneticist at the Institute for Systems Biology in Seattle. “We think that most people with bipolar disorder will have inherited several of these…risk variants.”

The bulk of a person’s risk for bipolar disorder comes from genetics, but only a quarter of that risk can be explained by common variations in genes. Roach’s team sequenced the genomes of 200 people from 41 families with a history of bipolar disorder. They then identified 164 rare forms of genes that show up more often in people with the condition. People with bipolar disorder had, on average, six of these rare forms, compared with just one, on average, found in their healthy relatives and the general population.

The identified genes control the ability of ions, or charged particles, to enter or leave nerve cells, or neurons. This affects neurons’ ability to pass information through the brain. Some of the gene variants probably increase how much neurons fire while others decrease it, the researchers say. Future research will need to explain what role these brain changes play in bipolar disorder.