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We Just Got Even More Evidence That Autism And Schizophrenia Share Genetic Roots

12 SEP 2018

Genetic changes that contribute to the development of autism in young children also appear to be responsible for schizophrenia, according to a number of studies conducted over the years.


While the body of evidence is convincing, it's still based largely on western populations. A new study from Japan backs up the hypothesis that the two disorders share genetic underpinnings in people from around the globe, revealing more details on the biochemistry behind them.

"The strength of our study is the systematic head-to-head comparison of pathogenic CNVs and biological pathways between autism spectrum disorder and schizophrenia," says senior author Norio Ozaki from Nagoya University Graduate School of Medicine.

It's now fairly apparent that there is considerable overlap in the genomic structures that can play an important role in the development of these two seemingly distinct disorders.

CNVs – or copy number variations – are repeating sections of chromosome that can arise when strings of DNA duplicate imperfectly.

The number of repeats varies significantly from person to person, but they're incredibly common structures. In fact, up to 10 percent of our genome could technically be classified as a CNV.

They're typically benign, but some replications can raise the risk of serious problems. For example, important genes nestled in between repeating fragments face a higher chance of being removed by a cell's editing machinery.


One example of this is when a region called 16p12.1 is accidentally removed this way. Combined with other mutations, such an edit can produce characteristics we refer to as autism. 

That's not to say a 16p12.1 deletion alone causes autism. Autism spectrum disorder (ASD) is a complex condition, its diagnosis based on a number of criteria dealing with impeded socialising and communication abilities and a tendency to be overstimulated.

Like ASD, schizophrenia has links with CNVs, yet it tends to be characterised by delusionary thinking and hallucinations rather than overstimulation and social challenges.

The more we learn about both conditions, the more complicated both seem. Like ASD, schizophrenia is also turning into a spectrum of conditions, some of which have more in common with autism than we'd thought.

It would be a stretch to say CNVs are primarily responsible here, since there are a variety of genetic and environmental influences that can produce the spectrum of traits.

But the presence of these CNVs does set the stage for mutations that are likely to contribute to the development of both conditions. What's more, it's looking likely that the very same CNVs are responsible for at least some of the neurological groundwork for each.


"Previous studies in Caucasian populations found overlap in pathogenic CNVs between the two disorders," says Ozaki.

"But their analyses were limited to a small number of genes and CNV loci."

The fact these analyses were based on a western population also left room for unsupported assumptions.

So the researchers gathered genomic information on 1,108 cases of ASD and 2,458 cases of schizophrenia from a Japanese population, comparing them with 2,095 controls.

Among around 8 percent of those with ASD or schizophrenia they identified rare examples of CNV, a figure that was significantly lower in the control group. Of those, about 29 locations on the chromosome (loci) were common to both disorders.

A closer look at the genetic changes brought on by these CNVs indicated they affected biochemical pathways associated with the metabolism of lipids and responses to oxidative stress – important factors in neurological development.

"The identification of shared pathways and disease-relevant genes provides biological insights into autism spectrum disorder and schizophrenia," says Ozaki.

Far from revealing the two conditions should belong in the same category, the research shows just how complicated the boundaries of disease are, and how subtle distinctions in genes and environment can give rise to vastly different experiences.

The researchers now plan on investigating similar overlaps in pathogenic CNVs in bipolar disorder, potentially revealing differences and similarities that might not only tell us how these complex conditions develop, but how a typical brain functions.

This research was published in Cell Reports.