A new study examines how Neandertal genes in the modern human genome may influence traits like depression and addiction.| Michael Smeltzer/ Vanderbilt University
In one of the first studies to directly compare the medical records of a large number of adults with their Neanderthal-derived DNA, researchers have confirmed that Neandertal genes have a subtle but significant impact on modern human biology.
"We discovered associations between Neandertal DNA and a wide range of traits in modern humans, including immunological, dermatological, neurological, psychiatric, and reproductive diseases," said senior author John Capra, assistant professor of biological sciences at Vanderbilt University.
Previous studies have suggested that when modern human populations migrated out of Africa, they interbred with Neandertals. More recently, scientists have identified parts of the human genome carrying Neandertal genetic variants, but — in part because Neandertal-derived DNA is so hard to identify and also because of the expense of performing tests for its influence on individuals — scientists still don't fully understand how Neandertal-derived variants influence modern human traits.
As Capra explained, "Determining the function of any bit of DNA, Neandertal or otherwise, is challenging. It often requires collecting a large number of people with a given trait and a similarly large number of people without the trait, looking at all of their genomes, and then testing for any places where those with the trait are more likely to have a given bit of DNA."
Vanderbilt University was well positioned to do this type of large-scale analysis, however. "Vanderbilt has a large database of anonymized electronic health records linked to genetic data from tens of thousands of patients at our hospital and others around the country," Capra explained. "This gave us an unprecedented ability to identify people with a vast range of traits and diseases, identify Neandertal DNA in their genomes, and then test whether the Neandertal DNA influenced any of the traits in their health records."
Through this approach, Capra and his colleagues — including Vanderbilt doctoral student Corinne Simonti, the paper's first author — found that Neandertal gene variants were significantly correlated with the risk for 12 traits. Some of the associations they uncovered, including the effect of Neandertal DNA on cells in the skin related to UV protection, confirm previous hypotheses.
Others were more intriguing. For example, Capra and colleagues found that a specific bit of Neandertal DNA significantly increases risk for nicotine addiction, and that a number of variants either positively or negatively influence the risk for depression.
"The influence of Neandertal DNA on depression risk was surprising," Capra said.
Given the association of Neandertal DNA with a skin phenotype intimately related to UV protection, and the role that sun exposure plays in depression in modern humans, it is possible that this influence of Neanderthal DNA has something to do with light exposure, Capra explained.
"It is important to note that depression is a very complex disease and also defined in the context of modern human societies, so we certainly can't say that our ancestors or Neanderthals were depressed in the modern sense. In my view though, this may point to an influence of Neanderthal DNA on behavior and mood," he said.
John Capra and Corinne Simonti at a press briefing at the 2016 AAAS Annual Meeting. | Boston Atlantic Photography
The pattern of associations his team discovered suggests that today's population retains Neandertal DNA that may have provided modern humans with adaptive advantages 40,000 years ago — as they migrated into new non-African environments with different pathogens and levels of sun exposure. However, many of these traits may no longer be advantageous in life today.
"The environments that most modern humans live in are very different than the conditions our ancestors faced 50,000 years ago," Capra said. "As a result, traits that might have been beneficial in adapting to challenging new non-African environments could easily be detrimental over the course of a long life without significant risk of infectious disease or starvation."
One example is a Neanderthal variant that increases blood coagulation.
"Increased coagulation could have helped our ancestors cope with new pathogens encountered in new environments by sealing wounds more quickly and generating a faster immune response," Capra said. "But in modern environments, the downsides to increased coagulation, such as increased risk of stroke and embolism, have become more apparent as we live longer lives."
There is still much to learn about the effects of interbreeding on different populations in recent human history. Capra said his team's next steps include expanding the study to bigger cohorts that contain groups of more diverse (not just European) ancestry.
"We hope that our approach will become a common analysis strategy in evolutionary genetics," he said.