Is the Autism Spectrum Also a Genetic Spectrum?

Genetics research into autism has made considerable strides in recent years. While it may seem to most lay people that a lot of funding goes into a field that has offered little translational help to those who want and need it, we are nevertheless coming closer to understanding precisely what is this group of very heterogeneous conditions, at which point I’m hopeful more interventions will reveal themselves once we have that foundation of knowledge.

We have learned a lot about rare autism syndromes that have strong genetic bases, which comprise an important minority of the spectrum. Unfortunately, it’s still a mystery how these rare syndromes may or may not relate to the rest of the autism spectrum.

A new article by  Rossi et al. (2017) suggests that the genes targeted in rare autism syndromes may in fact be involved in a  broader range of the autism spectrum than we’d anticipated.

The team performed exome sequencing on individuals with autism with intellectual disability, epilepsy, or psychiatric conditions, but who didn’t fit any already-recognized syndromes. Using in depth exome sequencing, they found that about 25% of those with autism or autism-like features had a positive genetic result, indicating that they had gene variants that were probable underlying causes of their autism.


Figure 2 from Rossi et al. (2017).

Most interesting of all was that the vast majority of the identified gene variants fell within genes that are already linked with rare autism syndromes. Therefore, even though these cases didn’t exhibit the full syndromes, the same genes were still affected.

The reasons for this are likely due to variations in mutation penetrance. Rare syndromes are often (though not always) the result of large deletion or duplication events, which are highly deleterious to the genes involved and are more likely to result in a consistent constellation of symptoms (i.e., a syndrome).

In contrast, a smaller mutation, such as a point mutation, is typically less deleterious to the functioning of a gene than a large deletion or duplication, and so production of the gene product may be only modestly impaired or the protein prone to misfolding, but it still may be capable of fulfilling some of its duties within the cell. Hence, the phenotype tends to be less severe. (This isn’t always the case, but is a general trend.)


While this study doesn’t address the question as to whether common variants (e.g., single nucleotide polymorphisms or SNPs) in these genes confer measurable autism risk, it does however suggest that a broader portion of the autism spectrum is affected by variants in syndromic genes.

I’m hoping over the next few years we’ll begin to address whether this is also the case for common variants– which are more likely to confer risk to a broader array of the spectrum, in combination with risks from the environment, such as maternal hormone disorders, immune dysfunction, and maternal stress.

3 responses to “Is the Autism Spectrum Also a Genetic Spectrum?

  1. I’ve noticed in my many years of practicing psychology that Prader-Willi Syndrome is frequently accompanied by autism. There is a genetic component to Prader-Willi and I wonder how close this is to one of many genetic markers for various forms of autism. Some of the eating habits of eating disordered autistic individuals (but not Prader-Willi) might also be linked to the genetics of the endocrine component such as a ghrelin problem, or something in the ventro-medial hypothalamus.

  2. There are certainly SNPs responsible for autism — when the environment triggers it. Shoenfeld says exactly the same thing about autoimmunity and there is no reason to believe it should be different for autism.

    Lyons-Weiler puts forth this equation in his book, the Environmental and Genetic Causes of Autism:

    Genetic(risk) + Environmental(risk) + G x E(risk) = Total(risk)

    There is something important to point out here: without the environmental trigger, two of the three terms on the left side of the formula fail. So, in the overwhelming number of cases, if there is no environmental trigger there will be no autism. For only a small portion of autistics is this not true (those with de novo mutations or those that rare damaging ones that are inherited, roughly 2% of autistics, see Gaugler et al, 2014); for the majority, the gun is loaded by genetics but it is the environment that pulls the trigger.

    As he points out in the book, “The Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-5) correctly refers to any discovered genetic basis of ASD as a risk factor or as a specifier, not a differential diagnostic marker that automatically denotes a private syndrome.”

    This work on genetics had to be done but now it’s long past time to turn our attention to the toxins in the environment that these people are unable to deal with as the source of the autism epidemic.

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