Neanderthal DNA May Whisper ‘Mood Disorder’ Over Millennia
Intriguing hints of a connection between Neanderthal DNA and modern-day depression may also point to new ways of using big data.
Perhaps it’s not quite right to blame psychiatric illness on ancestors who lived 50,000 years ago, but a recent story in Science reveals how far back in time lie the sources of modern disorders.
AP Photo/Martin Meissner
Genetic contributions from the Neanderthals preserved over the millennia appear to affect current risk of depression, tobacco use disorder, blood clotting, skin lesions, and other conditions, wrote John Capra, Ph.D., an assistant professor of biological sciences at Vanderbilt University; Corinne Simonti, B.S., a graduate student in Capra’s lab; and colleagues in the February 12 Science.
“We hope this leads to a better understanding of how humans evolved and the influences on how we get sick,” said Capra at a news briefing during the annual meeting of the American Association for the Advancement of Science in Washington, D.C., in February. “But the effects seen in modern environments do not tell us what these genes were doing 50,000 years ago.”
When anatomically modern humans moved out of Africa and into Europe and Asia, some of them met and mated with the Neanderthals. Present-day Eurasian populations contain an estimated 1 to 4 percent of Neanderthal DNA, and some alleles are found in modern humans at disproportionately higher than expected levels.
Neanderthals had lived in Europe and Asia for hundreds of thousands of years and so were well adapted to a colder climate and its pathogens. Offspring of the two populations thus might have been slightly better adapted in some ways to that environment, preserving Neanderthal DNA in the genome of modern humans.
Capra’s team compared high-resolution maps of Neanderthal haplotypes with data on 28,416 present-day humans from the Electronic Medical Records and Genomics (eMERGE) Network, a consortium linking genetic and medical diagnostic data from patients in seven academic medical centers across the United States.
Using genomewide complex trait analysis, they found significant but small contributions to risk of actinic keratosis (2.49 percent), mood disorders (0.68 percent), and depression (1.06 percent) from the Neanderthals. The Neanderthal alleles are enriched near genes known to be associated with depression, wrote Capra and Simonti.
A second approach, a phenomewide association study, also found associations with hypercoagulable state and tobacco use disorder.
The latter finding had nothing to do with tobacco, a New World plant. Rather, it is connected to a single-nucleotide polymorphism involved with reuptake of the neurotransmitter γ-aminobutyric acid (GABA).
In fact, the clinical significance of these associations varies considerably, Kenneth Kendler, M.D., a professor of psychiatry at Virginia Commonwealth University in Richmond, told Psychiatric News.
“We can speculate that an ability to have blood clot quickly would have been useful in the Paleolithic era, when the Neanhderthals were likely to pick up a lot of cuts and scrapes and infections,” said Kendler. “But it might not be so helpful today when we are more concerned about clotting in our arteries.”
However, the signals for psychiatric illnesses, while intriguing, are less strong, said Kendler. “There are some slight hints that our Neanderthal heritage might have introduced variants that affect the risk for depression and smoking, but there’s nothing more definitive.”
There was another lesson to be drawn from the encounter between ancient DNA and modern illness, said Capra.
“This kind of research shows how important it is to have large databases and for the scientific community to have access to them,” he said. “eMERGE was developed to understand the genetics of disease, not to study evolution.” ■
“The Phenotypic Legacy of Admixture Between Modern Humans and Neandertals” is posted at http://science.sciencemag.org/content/351/6274/737.full. A video of the news briefing with John Capra, Ph.D., and Corinne Simonti, B.S., can be accessed here.
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Published online: 28 March 2016
Published in print: March 19, 2016 – April 1, 2016
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