Neanderthal DNA linked to depression and nicotine addiction in modern humans

A study published in Science today has found that Neanderthal DNA has a significant influence on both physical and psychological traits in humans.

We talked to the study’s lead author John Capra, Assistant Professor in the Department of Biological Sciences and Biomedical Informatics at Vanderbilt University, to find out why depression, certain skin conditions, and blood clotting can all be linked to our ancient ancestors:

RG: What were the key findings from your study into the impact Neanderthal DNA has on modern human traits?

John Capra: The most important finding of our study is that Neanderthal DNA influences a broad range of traits relevant to disease risk in modern humans. When we started this study, we expected that, if we found any effects of Neanderthal DNA they would be on bodily systems that are involved in interactions with the environment. Several of our findings fit in well with this prediction. For example, we found that having Neanderthal DNA at one location in the genome significantly increased risk for blood hypercoagulation. Coagulation is one of most immediate immune responses to injury and potential infection, allowing wounds to heal quickly.

We also found that Neanderthal DNA significantly influenced risk for a skin disease called actinic keratosis that results in scaly skin lesions after long-term sun exposure, and we identified an association between Neanderthal DNA and a certain type of malnutrition.

In addition to these results, we also found several surprising associations between Neanderthal DNA and psychiatric and neurological phenotypes like depression and nicotine.

RG: Increased blood coagulation may have been a positive trait for Neanderthals, however today it is detrimental to health – causing strokes, for example. Why is this the case and why do we still carry these genes?

Capra: Many genetic variants, regardless of evolutionary origin and temporal context, are beneficial in some respects but detrimental in others. For example, consider the APOE4 allele, which increases the risk of Alzheimer’s, but may decrease the risk of other diseases in carriers.  So this phenomenon is by no means limited to Neanderthal DNA – our genomes keep around lots of mildly detrimental genetic variations. There are also many regions of the human genome where no one has any Neanderthal DNA, suggesting that many bits of Neanderthal DNA were removed from modern human genomes very quickly because they were very detrimental.

RG: You mention that one part of Neanderthal DNA significantly increases the risk for nicotine addiction. Do you know why this is? Did Neanderthals have access to nicotine?

Capra: Tobacco was found solely in the Western hemisphere until Europeans brought it back from expeditions to the Americas. While nicotine is present in plants other than tobacco, it is found in such small quantities as to be barely detectable. This is a great example of how the effects and interpretation of DNA variants are dependent on the environment. It is possible that this variant had an influence on a related trait that exhibited itself 50,000 years ago, but it is also possible that this is just an unfortunate effect that has become relevant in a modern environment.

RG: Can you explain more about the impact Neanderthal DNA has on chances of becoming depressed? Does this mean Neanderthals could have also suffered from depression?

Capra: In short: probably not. The longer answer is that depression is an incredibly complex disease and we don't fully understand the genetic and environmental drivers of depression today in modern populations. Thus, like nicotine addiction, depression might not even make sense as a "disease" 50,000 years ago. So it is possible that these variants had different effects on Neanderthals in their genetic and environmental background than they did on modern humans.

Furthermore, we found that some Neanderthal DNA increases the risk of depression in modern humans while a roughly similar number of specific Neanderthal DNA regions actually decrease the risk. This means that if I know what Neanderthal DNA you have, I can do a better job of predicting your risk for depression than if I don’t.

RG: Why did you choose to study this?

Capra: Previous work over the past several years using ancient DNA from fossils has demonstrated that anatomically modern humans interbred with older human forms, like Neanderthals, as they moved out of Africa 50–60,000 years ago. As a result of this, a small fraction (under two percent) of the genomes of most modern non-Africans is made up of DNA derived from Neanderthals. This raises several fascinating questions like: What effect does the Neanderthal DNA that remains in modern humans have on our biology? What do the effects of Neanderthal DNA tell us about the role of interbreeding in our species' history and evolution?

We realized that we had a great opportunity to answer these questions using large databases of anonymized versions of patient electronic health records linked to their genetic information. This way, we were able to investigate the effects of Neanderthal DNA in more than 28,000 adults from around the US.

RG: What are the next steps in your research?

Capra: There is still much to learn about the effects of interbreeding on different populations in recent human history. There are several next steps: 1) Expanding the study to bigger cohorts that contain groups of more diverse (not just European) ancestry. 2) Deriving more complex and detailed traits from the electronic health records. 3) Determining how Neanderthal DNA exerts its effects at the molecular level. 4) Developing better models for how selection has acted on Neanderthal DNA after interbreeding.

Featured image courtesy of Jaroslav A. Polák