Ancient Neanderthal DNA found to influence autism susceptibility

A recent study published in Molecular psychiatry reveals that certain genetic traits inherited from Neanderthals may contribute significantly to the development of autism. This groundbreaking research shows that specific genetic variants in Neanderthals can influence susceptibility to autism, suggesting a link between our ancient relatives and modern neurodevelopmental conditions.

The study was motivated by long-standing curiosity about how archaic human DNA, particularly from Neanderthals, affects modern human health. Homo neanderthalensis, commonly known as Neanderthals, are our closest known cousins ​​on the hominin tree of life. Populations of European and Asian descent are estimated to have about 2% Neanderthal DNA, a holdover from interbreeding events that occurred when anatomically modern humans migrated out of Africa about 47,000 to 65,000 years ago.

While previous studies have identified Neanderthal genetic contributions to traits such as immune function, skin pigmentation and metabolism, the role of these ancient genes in brain development and neurodevelopmental conditions such as autism has remained largely unexplored. In their new study, the researchers aimed to fill this gap by investigating whether Neanderthal DNA is more prevalent in autistic individuals compared to non-autistic controls.

Autism is a neurodevelopmental condition characterized by challenges in social interaction, communication, and repetitive behaviors or restricted interests. The severity and specific manifestations of these traits can vary widely among individuals. Given that autism is characterized by distinct patterns in brain connectivity, the researchers sought to better understand whether these patterns could be linked to Neanderthal DNA.

“I have to say that I am on the autism spectrum myself. I have been involved in the online autism and neurodiversity communities since 2003. I was a moderator on the popular forum, Wrong Planet, under the handle, ‘Sophist’ and later created my own autism website called Gestalt, ” explained the study. author Emily Casanova, an assistant professor of neuroscience at Loyola University New Orleans and creator of the website Science Over a Cuppa.

“So I’ve been interested in autism and understanding what makes it grow for a long time. In the last decade, I’ve focused more on the genetic side, but I’ve also had an ongoing interest in evolutionary biology. For many years, this last interest was just a hobby, but in recent years I’ve started working more on things like studying the evolution of autism genes and just trying to understand how many of these genes are linked. with development they evolve over time.”

“You may be wondering what this has to do with Neanderthals! Well, one of the topics I’ve been studying is how hybridization (the joining of two species) affects the offspring of subsequent generations,” Casanova continued. “Hybridization has a tendency to ‘shake things up’ genetically—not just because you’re joining two species together in an additive process—but because some genetic variants don’t always work so well when they’re suddenly merged into a single genome. “

“Variants tend to have partners they like to ‘travel’ with over the generations, and when sexual recombination separates them, it can sometimes create some new problems in the offspring. Interestingly, this process may also be a stimulus for faster evolution after hybridization.

“So I’m very interested in these Neanderthal variants – not only in understanding how they might affect susceptibility to autism, but also how they might have guided our subsequent brain evolution over the last 50,000 years ,” she explained. “I don’t think it’s a coincidence that many of the variants implicated in autism are also implicated in human intelligence, so I find this possibility fascinating.”

The research team used whole exome sequencing (WES) data from the Simons Foundation Powering Autism Research (SPARK) Database, focusing on autistic individuals and their unaffected siblings. They compared these groups with individuals from the Genotype-Tissue Expression (GTEx) and 1000 Genomes (1000G) databases. Specifically, the researchers examined Neanderthal-derived single nucleotide polymorphisms (SNPs), which are variations in a single DNA building block.

The researchers found that autistic individuals had a higher prevalence of rare Neanderthal genetic variants compared to non-autistic controls. These rare variants, which occur in less than 1% of the population, were significantly enriched in the genomes of autistic individuals in three major ethnic groups: non-Hispanic blacks, Hispanic whites, and non-Hispanic whites.

“I know a lot of people will read the headline and immediately assume that autistic people have more Neanderthal DNA than non-autistic people — that they’re somehow ‘more Neanderthal,'” Casanova told PsyPost. “I wouldn’t say I blame them for the assumption, especially when the ‘Neanderthal Theory of Autism’ had already been proposed and popularized by Leif Ekblad, an independent autistic researcher, as early as 2001. This idea made its way around the autistic community online in the early 2000s and served in part as the inspiration for Ekblad’s Aspie Quiz, which has gone on to be one of the most popular online autism quizzes.

“Our results are a little more nuanced than ‘autistic people are just more Neanderthals.'” By way of background, the human genome consists of over 3 billion nucleotide pairs. The vast majority of our genomes are pretty much identical to each other. But there are some places in the human genome that are sites of variation.”

“Neanderthal DNA offers some of those variants, and some of those variants are common (1% or more of the population have that particular variant) or may be rare (less than 1% have that variant ),” Casanova explained. “In our study, we found that autistic people, on average, have more rare Neanderthal variants, not that they have more Neanderthal DNA in general. This means that while not all Neanderthal DNA is necessarily influencing autism susceptibility, a subset is.”

In contrast to rare variants, the study found that common Neanderthal-derived variants were less prevalent in non-Hispanic black and Hispanic white autistic individuals compared to controls. Common variants are those present in 1% or more of the population. This finding was not observed in non-Hispanic white autistic individuals, who did not show significant differences in common Neanderthal DNA compared to controls or unaffected siblings.

The researchers also identified specific clinical associations between Neanderthal-derived variants and autism-related traits. For example, a particular SNP (rs112406029) in the SLC37A1 gene was significantly associated with epilepsy in non-Hispanic white autistic individuals. This variant was more common in autistic individuals with epilepsy than in those without epilepsy and was even more prevalent in those with a family history of the condition.

Similar associations were found in other ethnic groups, linking some Neanderthal variants to traits such as intellectual disability, language delay and language regression. These findings suggest that Neanderthal-derived genetic variants may not only contribute to autism susceptibility, but also influence specific comorbid conditions and traits.

“I was very surprised that many of the Neanderthal-derived variants we found that were associated with autism differed dramatically by ethnic group,” Casanova said. “In hindsight, I think this shouldn’t be that surprising, but it does mean that many of these weak variants that play roles in autism are influenced by the background genome, which varies by ethnicity.”

“So one variant may be strongly associated with autism in black Americans, while the same variant does not appear to be playing a measurable role in white Hispanics and non-Hispanics. To me this suggests that our tendency to ‘whitewash’ genetics and ignore variants that are not implicated in all genetic backgrounds means that we are missing many important genetic factors.”

The findings have important implications for our understanding of autism and its genetic underpinnings. By highlighting the role of ancient Neanderthal DNA, the research opens new avenues to explore how hybridization events between archaic and modern humans shaped neurodevelopmental conditions.

“In this current study, we investigated only the parts of the genome that contain protein-coding genes (known as the exome),” Casanova noted. “In the next phase, we plan to look at the entire genome, as there is a lot of interesting regulatory material contained in those regions that obviously affect when and how genes are expressed. We also plan to include the Denisovan genome in our next phase of study to see if that DNA may play a role in autism in people of Asian/Native American descent.

“Some people in the autism community are uncomfortable with genetic studies,” the researcher added. “Partly, this is rooted in the fear associated with eugenics. The autistic community is aware of how prenatal genotyping of Down Syndrome has led to miscarriage in about 30% of these cases. But I just want to reassure people that these Neanderthal-derived variants are also occurring in people, especially family members, without autism. So while identifying these susceptibility factors can help us build a more complete picture of autism and its very complex roots, this knowledge cannot be used to aid eugenics or similar agendas.”

The study, “Enrichment of a subset of Neanderthal polymorphisms in autistic relatives and siblings,” Rini Pauly, Layla Johnson, F. Alex Feltus, and Emily L. Casanova.