As science continues to decode the human genome, our knowledge of the genetic components of disease is advancing at exponential rates. Research has even pinpointed single defective genes that cause some rare diseases, such as Huntington’s disease, cystic fibrosis and some types of muscular dystrophy. More common disorders, like high blood pressure, diabetes and mental illnesses such as depression, however, are not caused by a single or even multiple genetic anomalies. There is, as far as anyone knows, no “depression gene.” And no one therefore inherits depression from his or her parents.
But there is a clear genetic component of depression. Studies of twins, for example, have found that if one twin has depression, the other is much more likely to have it as well compared to non-twin siblings. “We know there is a heritable quality of both unipolar and bipolar depression,” says Dr. John H. Krystal, chair of the department of psychiatry at Yale University School of Medicine and chief of psychiatry at Yale-New Haven Hospital. It is not known exactly how strong that heritable factor is, but it is estimated at somewhere between one-third and one-half of the reason someone may develop the disease. “A bit more than half the risk comes from stressful inutero or life events,” Krystal says. “If you don’t have a family history of depression, then it tends to develop only in the context of stress.”
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If this sounds a bit vague, that’s because it is. “The genetics of depression are a very difficult area to study,” he says. Blame this, at least in part, on statistics. “With other disorders, like schizophrenia or autism, you know there is a strong genetic signal, and you expect to see it, but even then you need enormously large samples to identify the genes [for those diseases],” Krystal says. Dr. Steven E. Hyman, director of the Stanley Center for Psychiatric Research at Broad Institute of MIT and Harvard and professor of stem cell and regenerative biology at Harvard University, says that genetics research is most advanced for schizophrenia — about 80 percent of the risk for schizophrenia is related to genes, he says — and a bit further behind for bipolar and autism spectrum disorders. “Depression research is succeeding, but it is at a very early stage,” he says. “People have multiple different etiologies [causes or set of causes], so we need a very large cohort to overcome that statistical noise.”
But that noise is starting to be reduced. “The first genetic findings are emerging,” Hyman says.
15 Genetic Regions Linked to Depression
For the first time, researchers are acquiring data from large enough study samples to begin to identify the set of genes associated with the heritable risk for depression. For this, you can thank the genetics company 23andMe, which takes saliva samples and analyzes DNA for genetic health risks and ancestry. A 2016 study used data from 23andMe on more than 75,000 individuals with European ancestry who self-reported a clinical diagnosis of depression and more than 231,000 individuals reporting no history of depression. The researchers were able to locate 15 regions in the genome that were associated with depression.
And those findings were replicated in another sample of 45,000 cases of depression, Krystal says. “Replicability is so fundamental to validity, and for the first time we are getting this replicability, which suggests in some ways this is the start of a new era for understanding the genetic risk factors for depression.”
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That understanding should increase soon. In August 2017, 23andMe announced they were looking to enroll 15,000 people with depression and 10,000 others with bipolar disorder for another study to untangle how genetics and environment combine to influence mental health and illness. But identifying the genes associated with depression, while an important step, is only the first of many. “We don’t know how [these genes] are implicated in risk. That is still being worked out,” Krystal says. “But if you don’t know what genes to study, you never find the path to follow. These genes are going to get a lot of intensive study.”
Streams of Information Converging
Still, it’s unlikely there will ever be a single genetic marker for depression. “As genes get discovered, and they are being discovered, you don’t say ‘aha,'” Hyman says. “Any person might have any combination of risk-associated variance, but across even similar populations there are many, many genetic paths to depression. So it is certainly not likely there will ever be a diagnostic test that is purely genetic.”
However, he says, as science discovers enough of these small genetic changes, “you can begin to count how many risk versions someone might have, so as a statistical matter you have a higher genetic risk for depression. It is a bit like cardiovascular disease. There clearly is some genetic risk, but then there is also risk from high lipids, from high blood pressure, from smoking — and a risk predictor is actually a sum of all these factors.”
[See: Am I Just Sad — or Actually Depressed?]
There are also a number of nongenetic risk factors for depression, such as stress, nutrition and exercise, to be sorted out. And without that knowledge, “it is harder to predict who has flavor X of depression,” Hyman says. “Nonetheless, with all those caveats, looking at genetic loading let’s say three to five years from now, we will be able to at least stratify people.” Despite all that is yet to be learned, “I am more than hopeful that, with enough time and effort, genetics will yield a useful piece of the puzzle,” Hyman says. Krystal agrees with this positive forecast. Genetics, he says, is “another part of a converging tide of many different streams coming together in new and informative ways.”
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What Do We Know About Genetic Links to Depression? originally appeared on usnews.com