Neanderthal DNA May Provide Clues About the Genetic Risks for Brain Disorders and Addiction

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Summary: Traits with the strongest Neanderthal DNA contribution were sleeping patterns, smoking habits and alcohol consumption.

Source: Estonian Research Council

Human brain disorders such as neurological or psychiatric diseases have long been known to run in families, suggesting some heredity. In accordance with this hypothesis, genetic risk factors for developing these diseases have been identified.

However, fundamental questions about the evolutionary drivers have remained elusive. In other words, why have genetic variants that increase the risk for diseases not been eliminated in the course of evolution?

Answering these questions was notoriously difficult. However, new discoveries about events in the deep human past have given scientists new tools to begin to unravel these mysteries: when modern humans moved out of Africa more than 60,000 years ago, they met and mixed with other archaic humans such as Neanderthals.

About 40% of the Neanderthal genome is still found in contemporary non-Africans, and each individual still has ~2% of Neanderthal DNA. Some of the archaic genetic variants may have conferred advantages at some point in our evolutionary past.

Today, scientists can use this information to learn more about the influence of these genetic variants on human behavior and the risk of developing diseases.

Using this approach, a new study by an international team led by researchers from the University of Tartu, Charité Berlin and the Amsterdam UMC analyzed Neandertal DNA associations with a wide variety of more than a hundred brain disorders and traits such as sleep, smoking or alcohol use in the UK Biobank with the aim of delineating the specific contribution of Neandertal DNA to variation in behavioral traits in humans today.

The study found that although Neanderthal DNA showed disproportionate numbers of associations with various traits associated with diseases of the central nervous system, the diseases themselves did not show significant numbers of Neanderthal DNA associations.

Among the traits with the strongest Neanderthal DNA contribution were smoking habits, alcohol consumption and sleeping patterns. Using data from other cohorts such as the Estonian Biobank, the Netherlands Study of Depression and Anxiety, FinnGen, Biobank Japan and deCode, several of these results could be replicated.

Of specific note were two independent top-risk Neanderthal variants for a positive smoking status that were found in the UK Biobank and Biobank Japan respectively.

“Our results suggest that Neanderthals carried multiple variants that significantly increase smoking risk in humans today. It remains unclear what phenotypic effects these variants had in Neanderthals.

“However, these results provide interesting candidates for further functional testing and will potentially help us in the future to better understand Neandertal-specific biology,” said Michael Dannemann, associate professor of evolutionary genomics at the University of Tartu and the lead author of this study

“The important associations of Neandertal DNA with alcohol and smoking habits can help us to discover the evolutionary origins of addictive and reward-seeking behavior,” added Stefan M Gold, professor of neuropsychiatry at Charité, Berlin, who co-led this study.

About 40% of the Neanderthal genome is still found in contemporary non-Africans, and each individual still has ~2% of Neanderthal DNA. Image is in the public domain

“It is important to note that sleep problems, alcohol and nicotine use have consistently been identified as common risk factors for a variety of neurological and psychiatric disorders. On the other hand, there are some intriguing findings from anthropology that show some social benefits of higher tolerance to these substances in hunter-gatherers have been suggested.

“Thus, our findings support the hypothesis that it is not brain diseases themselves that have evolutionary explanations, but that natural selection shapes traits that make us vulnerable to them in the modern context.”

“Neanderthals populated parts of Eurasia more than 100,000 years before modern humans left Africa to populate the rest of the world. The high frequency of some of the variants associated with varying sleep patterns may suggest that these would have been beneficial outside of Africa—an environment defined, for example, by different levels of seasonality and UV light exposure than the environment that modern humans evolved in,” Dannemann added.

About this news about genetics and evolutionary neuroscience research

Writer: Carlos Kuiv
Source: Estonian Research Council
Contact: Carlos Kuiv – Estonian Research Council
Image: The image is in the public domain

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Original research: Free access.
“Neanderthal introgression shares the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes” by Michael Dannemann et al. Translational Psychiatry


Neanderthal introgression shares the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes

Despite progress in identifying the genetic basis of psychiatric and neurological disorders, fundamental questions about their evolutionary origins remain elusive.

Here, introgressed variants of archaic humans such as Neanderthals can serve as an intriguing research paradigm.

We compared the number of associations for Neanderthal variants with the number of associations of frequency-adjusted non-archaic variants with respect to human CNS disorders (neurological and psychiatric), nervous system drugs (as a proxy for disease), and related, non-disease phenotypes in the UK biobank (UKBB).

While no enrichment for Neandertal genetic variants was observed in the UKBB for psychiatric or neurological disease categories, we found significant associations with certain behavioral phenotypes, including pain, chronotype/sleep, smoking and alcohol consumption.

In some cases, the enrichment signal was driven by Neanderthal variants that represented the strongest association genome-wide. SNPs within a Neanderthal haplotype associated with smoking in the UKBB could be replicated in four independent genomic datasets.

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