Why are brain disorders at genetic risk? Neanderthal DNA may provide some answers

It has long been known that human brain diseases such as neurological or psychiatric disorders can occur in families, suggesting that there is a certain hereditary nature
.
Consistent with this hypothesis, the genetic risk factors that contribute to these diseases have been identified
.
However, fundamental questions about evolutionary drivers remain elusive
.
In other words, why have genetic variants that increase the risk of disease not been eliminated during evolution?

Answering these questions is notoriously difficult
.
However, new discoveries about the deeper events of human history have given scientists new tools to begin to solve these mysteries: when modern humans left Africa 60,000 years ago, they encountered and mixed
with other ancient humans, such as Neanderthals.
About 40 percent of the Neanderthal genome can still be found in non-Africans today, and each person still carries about 2 percent of Neanderthal DNA
.
Some ancient genetic variants may have brought benefits
at some point in our evolutionary history.

Today, scientists can use this information to learn more about the effects of these genetic variants on human behavior and the risk of
developing disease.
Using this approach, an international team led by researchers at the University of Tartu, Charité Berlin and UMC Amsterdam conducted a new study analyzing the relationship between Neanderthal DNA and more than 100 brain diseases and traits in the British Biobank, such as sleep, smoking or drinking, with the aim of narrowing the specific contribution
of Neanderthal DNA to changes in human behavior today 。 The study found that while Neanderthal DNA showed excessive associations with several traits associated with central nervous system disorders, the diseases themselves did not show any significant Neanderthal DNA associations
.
The most strongly contributed traits to Neanderthal DNA include smoking habits, drinking alcohol, and sleep patterns
.
Using data from other cohorts, such as the Estonian Biobank, the Netherlands Depression and Anxiety Study, FinnGen, BioBank of Japan, and deCode, some of the results can be replicated
.

Of particular note is the discovery of two independent high-risk Neanderthal variants with smoking positive status in the Biobank of the United Kingdom and the Biobank of Japan
, respectively.
"Our findings suggest that Neanderthals carry multiple variant genes that greatly increase the risk of smoking in
modern humans.
" The phenotypic effect
of these variants on Neanderthals is unclear.
However, these results provide interesting candidates for further functional testing and may help us better understand Neanderthal-specific biology in the future," said
Michael Danneman, associate professor of evolutionary genomics at the University of Tartu and lead author of the study.
"The remarkable link between Neanderthal DNA and alcohol and smoking habits may help us unlock the evolutionary origins of addiction and reward-seeking behavior," said Stefan Berger, a professor of neuropsychiatry at Charité Berlin.
M.
Gold added that he was co-chair
of the study.
"It's worth noting that sleep problems, alcohol and nicotine use have long been identified as common risk factors
for a range of neurological and psychiatric disorders.

On the other hand, some interesting findings from anthropology suggest that hunter-gatherer tolerance to these substances has some social benefits
.
Thus, our findings support the hypothesis that it is not that brain diseases themselves have an evolutionary explanation, but that natural selection has shaped traits that make us susceptible to them in modern settings
.
"Neanderthals settled in parts of Eurasia more than 100,000 years ago as early as modern humans left Africa to settle in other parts of the
world.
The high frequency of some of the variants associated with different sleep patterns may indicate that these variants are advantageous in environments outside of Africa – for example, the African environment is defined by varying degrees of seasonal and ultraviolet exposure compared to the environment in which modern humans evolved," Dannemann added
.