Genome-wide association study identifies gene linked to seasonal affective disorder

A genome-wide association study (GWAS) of genetic risk factors for seasonal affective disorder has identified a gene that might contribute to the condition. The research has been published in Translational Psychiatry.

“I have seen a number of patients who told me about how their mood drops in the middle of October as the days grow shorter and darkness falls,” explained study author James Bennett Potash of Johns Hopkins Medicine.

“Several of them have said they did much better living in Arizona or South Florida. It is striking that in our data on close to 4,000 people with depression or bipolar disorder, about one-third of them say their depressions tend to start or get worse in fall or winter.”

Genome-wide association studies analyze large collections of genomes to determine whether particular genetic variants are associated with a particular trait. In the current study, the researchers examined 1,380 cases of Americans with SAD and 2,937 individuals without SAD.

They found one gene that could be related to a heightened risk of seasonal depression.

“A substantial minority of people with mood disorders do have depression that is seasonal. We have known this for awhile now and our study supports it,” Potash told PsyPost.

“We have also known that this tendency in some people for depression to be worse as the days grow shorter is in part determined by people’s genetic make-up. What our study adds is a clue about one of the genes that might explain this tendency, a gene that goes by the name of ZBTB20. This gene provides the blueprint for a protein that, at least in mice, is involved in circadian rhythms, and in adjustment of behavior to shortened days.”

The study — like all research — has some limitations.

“As with many studies of this kind, these results are not definitive. First, we need additional studies to see whether the same observations can be replicated in other large samples of people with seasonal affective disorder. That would reassure us that our results are real and not just a fluke,” Potash explained.

“Second, we would want to see whether the variation in the ZBTB20 gene that we have focused on is associated with a change in how the brain functions. We want to know how the change in the gene might lead to a change in mood and behavior.”

“Depression is the most common serious psychiatric disorder,” Potash added. “Though we have good treatments for it, there remain a large chunk of people who do not respond to what we currently have to offer. We need better treatments, and the way we will get there is through research that gets us to a fundamental understanding of the mechanisms in the brain that set this illness in motion and sustain it.”

“I am grateful that we are finally making inroads here, as genetic studies just in the last several years have begun to robustly identify key molecular players in risk for mood disorders. Much progress has been made by pooling together ever larger samples of DNA from people with mood disorders. There is still room to make progress too through looking at subtypes of illness, such as people with seasonal mood, or affective, disorder.”

The study, “Genome-wide association study of seasonal affective disorder“, was authored by Kwo Wei David Ho, Shizhong Han, Jakob V. Nielsen, Dubravka Jancic, Benjamin Hing, Jess Fiedorowicz, Myrna M. Weissman, Douglas F. Levinson, and James B. Potash