Neandertal DNA May Provide Answers to Brain Disorder Genetic Risks

Author: Estonian Research Council
Published: 2022/10/06 - Updated: 2023/01/04
Peer Reviewed Publication: Yes
Category Topic: Anthropology - Related Publications

Page Content: Synopsis - Introduction - Main

Synopsis: The study analyzed Neandertal DNA associations with a large variety of more than a hundred brain disorders and traits such as sleep, smoking, or alcohol use. Around 40% of the Neandertal genome can still be found in present-day non-Africans, and each individual still carries ~2% of Neandertal DNA.

Defining Neandertals

Neandertals

Neandertals, Homo neanderthalensis or Homo sapiens neanderthalensis, is an extinct species of archaic humans living in Eurasia until about 40,000 years ago. While the "causes of Neanderthal disappearance about 40,000 years ago remain highly contested," demographic factors like small population size, inbreeding, and random fluctuations are considered likely factors. Other scholars have proposed competitive replacement, assimilation into the modern human genome (bred into extinction), significant climatic change, disease, or a combination of these factors.

What is the difference between Neanderthal and Neandertal? A few scientific publications prefer Neandertal. Neanderthal, the original spelling, was derived from the German valley where Neanderthal fossils were first discovered in the 19th century. In 1901, however, the German name of the valley was officially changed to Neandertal.

Introduction

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

It has been known for a long time that human brain disorders, such as neurological or psychiatric diseases, run in families, suggesting some heritability. In line with this hypothesis, genetic risk factors for developing these illnesses have been identified. However, fundamental questions about the evolutionary drivers have remained elusive. In other words, why are genetic variants that increase the risk of diseases not eliminated in evolution?

Main Content

To answer these questions has been notoriously difficult. However, discoveries about events in the deep human past have handed scientists new tools to start to unravel these mysteries: when modern humans moved out of Africa >60,000 years ago, they met and mixed with other archaic humans such as Neandertals. Around 40% of the Neandertal genome can still be found in present-day non-Africans, and each individual still carries ~2% of Neandertal DNA. Some archaic genetic variants may have conferred benefits 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 from an international team led by researchers from the University of Tartu, Charité Berlin, and the Amsterdam UMC analyzed Neandertal DNA associations with a large variety of more than a hundred brain disorders and traits such as sleep, smoking or alcohol use in the UK Biobank to narrow down the specific contribution of Neandertal DNA to variation in behavioral features in people today.

The study found that while Neandertal DNA showed over-proportional numbers of associations with several traits associated with central nervous system diseases, the diseases did not show any significant numbers of Neandertal DNA associations. Among the traits with the strongest Neandertal DNA contribution were smoking habits, alcohol consumption, and sleeping patterns. Several of these results could be replicated using data from other cohorts such as the Estonian Biobank, the Netherlands Study of Depression and Anxiety, FinnGen, Biobank Japan, and deCode. Of specific note were two independent top-risk Neandertal variants for a positive smoking status found in the UK Biobank and Biobank Japan, respectively.

"Our results suggest that Neandertals carried multiple variants that substantially increase the smoking risk in people today. It remains unclear what phenotypic effects these variants had in Neandertals. 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 significant associations of Neandertal DNA with alcohol and smoking habits might help us to unravel the evolutionary origin of addictive and reward-seeking behavior," added Stefan M Gold, professor of neuropsychiatry at Charité, Berlin, who co-led this study. "It is important to note that sleep problems and alcohol and nicotine use have consistently been identified as common risk factors for various neurological and psychiatric disorders. On the other hand, some intriguing findings from anthropology have suggested some social benefits of higher tolerance to these substances in hunter-gatherers. Thus, our findings support the hypothesis that it is not brain diseases that have evolutionary explanations but that natural selection shapes traits that make us vulnerable to them in the modern context."

"Neandertals populated parts of Eurasia already more than 100,000 years before modern humans went out of Africa to populate the rest of the world. The high frequency of some of the variants that are associated with varying sleeping patterns might suggest that these have been advantageous outside of Africa - an environment that is defined, for example, by different levels of seasonality and UV light exposures than the environment that modern humans evolved in," added Dannemann.

Related Information

Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Estonian Research Council and published on 2022/10/06, this content may have been edited for style, clarity, or brevity.