Emerging research suggests a DNA region on chromosome 3 is related to depression.
Two independent studies, one from Washington University School of Medicine in St. Louis and the other from King’s College London, identify a DNA region containing up to 90 genes. Both studies are published in the American Journal of Psychiatry.
Major depression affects approximately 20 percent of people at some point during their lives, and family studies have long suggested that depression risk is influenced by genetics.
“What’s remarkable is that both groups found exactly the same region in two separate studies,” said senior investigator Pamela A. F. Madden, Ph.D., professor of psychiatry at Washington University. “We were working independently and not collaborating on any level, but as we looked for ways to replicate our findings, the group in London contacted us to say, ‘We have the same linkage peak, and it’s significant.’”
Madden and the other researchers believe it is likely that many genes are involved in depression. While the new findings won’t benefit patients immediately, the discovery is an important step toward understanding what may be happening at the genetic and molecular levels, she says.
The group at King’s College London followed more than 800 families in the United Kingdom affected by recurrent depression. The Washington University group gathered data from 91 families in Australia and another 25 families in Finland.
At least two siblings in each family had a history of depression, but the Australian and Finnish participants were studied originally because they were heavy smokers.
“Major depression is more common in smokers, with lifetime reports as high as 60 percent in smokers seeking treatment,” said lead author Michele L. Pergadia, Ph.D., research assistant professor of psychiatry at Washington University.
“Smokers with depression tend to experience more nicotine withdrawal and may be more likely to relapse when trying to quit. Previous studies suggest that smoking and depression run together in families. In our study, we detected a region of the genome that travels with depression in families of smokers.”
English researchers were focusing on individuals with recurrent depression.
“These findings are truly exciting,” said Gerome Breen, Ph.D., lead author of the King’s College London study. “For the first time, we have found a genetic region associated with depression, and what makes the findings striking is the similarity of the results between our studies.”
From two different data sets, gathered for different purposes and studied in different ways, the research teams found what is known as a linkage peak on chromosome 3.
That means that the depressed siblings in the families in both studies carried many of the same genetic variations in that particular DNA region.
Unlike many genetic findings, this particular DNA region has genome-wide significance. Often when researchers correct statistically for looking across the entire genome, what appeared originally to be significant becomes much less so. That was not the case with these studies.
“Our linkage findings highlight a broad area,” Pergadia said. “I think we’re just beginning to make our way through the maze of influences on depression. The U.K. samples came from families known to be affected by depression. Our samples came from heavy smokers, so one thing we might do as we move forward is try to better characterize these families, to learn more about their smoking and depression histories, in addition to all of their genetic information in this area.”
Pergadia said it may be worthwhile to start by combining the data sets from the two studies to see whether this region of chromosome 3 continues to exert a significant effect.
Although there is still work to do, the new studies are a very important step on the road to understanding how genes influence depression, according to Peter McGuffin, M.B., Ph.D., director of the Medical Research Council Social, Genetic and Developmental Psychiatry Centre at King’s College London.
“The findings are ground-breaking,” said McGuffin, senior author of that study. “However, they still only account for a small proportion of the genetic risk for depression. More and larger studies will be required to find the other parts of the genome involved.”