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Neanderthal DNA may provide clues to genetic risks for brain disorders and addiction

Summary: The traits with the strongest contribution to Neanderthal DNA were sleep patterns, smoking habits, and alcohol consumption.

Source: Estonian Research Council

It has long been known that disorders of the human brain such as neurological or psychiatric diseases are hereditary, suggesting some heritability. In line with this hypothesis, genetic risk factors for the development of these diseases have been identified.

However, fundamental questions about the drivers of evolution have remained elusive. In other words, why aren’t genetic variants that increase disease risk eliminated during evolution?

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

About 40% of the Neanderthal genome is still found in non-Africans today, and each individual still carries about 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 impact 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 UMC Amsterdam analyzed the associations of Neanderthal DNA with a wide variety of more of a hundred brain disorders and traits such as sleep, smoking or alcohol. use in the UK Biobank with the aim of reducing the specific contribution of Neanderthal DNA to variation in behavioral characteristics in people today.

The study found that while Neanderthal DNA showed an overproportionate number of associations with several traits associated with central nervous system diseases, the diseases themselves showed no significant number of Neanderthal DNA associations.

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

Of particular note are two independent high-risk Neanderthal variants for positive smoking status that were found in the UK Biobank and the Japanese Biobank, respectively.

“Our results suggest that Neanderthals carried multiple variants that significantly increase the risk of smoking in people 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 specific Neanderthal biology,” said Michael Dannemann, associate professor of evolutionary genomics at the University of Tartu and lead author of this study. .

“The significant associations of Neanderthal DNA with alcohol and smoking habits could help us untangle the evolutionary origin of addictive and reward-seeking behavior,” added Charité Professor of Neuropsychiatry Stefan M Gold. Berlin, who co-directed this study.

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

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

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

“Neanderthals populated parts of Eurasia already over 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 variable sleep patterns might suggest that these have been advantageous outside of Africa – an environment that is defined, for example, by different levels of seasonality and radiation exposure. UV as the environment that modern humans evolved,” added Dannemann.

About this genetics and evolutionary neuroscience research news

Author: carlos dry
Source: Estonian Research Council
Contact: Carlos Kuiv – Estonian Research Council
Image: Image is in public domain

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


Summary

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

Despite advances 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 to the number of associations of frequency-matched non-archaic variants with respect to human CNS disorders (neurological and psychiatric), nervous system drug prescriptions (as an indicator of disease) and related non-archaic disorders. -Disease phenotypes in the UK Biobank (UKBB).

Although no enrichment for Neanderthal 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 genome-wide association. SNPs within a smoking-associated Neanderthal haplotype in the UKBB could be replicated in four independent genomic datasets.

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