Concerns about genetic testing for autism/ASD

Autistic spectrum disorder (ASD) is a collective term for neurodevelopmental problems involving social & communication deficits as well as restricted and repetitive behaviours. Scores of studies over the past couple of decades consistently agree that genetics play a very important role in this condition (with estimates of heritability around about 80%).

Naturally, this observation has opened up a floodgate of research trying to hunt down the genetic factors that may be involved. The genetics of such a complex and variable condition, however, are (unsurprisingly) incredibly complicated. It’s quite clear that there is no “gene for autism/ASD” – there is no one, single genetic factor which can explain every single case of ASD. There are also environmental factors involved, as well as epigenetic changes (where the structure of DNA is unaffected but what genes actually get expressed (i.e. used) in the body is changed). But the story is still not that simple. There are likely to be a good deal of genetic factors involved (some estimate over 1000), most likely interacting together within biological systems (known as gene x gene interaction). What’s more, the exact pattern of which of these genetic factors are involved is likely to differ from individual to individual. This is complementary to the variability of symptoms of ASD and associated difficulties, from each autistic person to the next. As the saying goes, “if you’ve met one individual with autism, you’ve met one individual with autism”.

I’ve read a fair amount on the subject, but I’m relatively new to this field and I’m certainly no expert. Nonetheless, I was mildly concerned when I read a recent post on the SFARI website about a “new diagnostic” test for ASD. The test apparently involves Next Generation Sequencing (NGS) in an attempt to examine an autistic individual’s DNA for point mutations of single nucleotides within 62 genes that have some small level of support in possibly being implicated in some cases of ASD. NGS sounds fancy and expensive. That’s partly because it is a very new (and exciting) technique and as such, it genuinely is quite costly – though getting cheaper by the moment.

However, all the reading & literature searching I’ve been doing over the last few months on the genetics of ASD makes me a little worried about what possible benefit individuals with ASD and their parents could actually get out of this particular “test”. More established cytogenetic tests for gross chromosomal abnormalities, such as fragile X, which have been around for a while, already have a body of robust scientific research and seem to have real-life implications and clinical applications. However, NGS is quite different and as it is a pretty new technique, there is not enough robust evidence out there yet to definitively implicate any particular factors in ASD, much less definitively implicate all of those 62 genes. 3 very recent exciting studies published in Nature (discussed quite well here, here and here) are the biggest ones to date using NGS to investigate ASD; yet still the specific genetic mutations they implicate are far from being definitely confirmed as risks for the condition. Their effect sizes are quite small and some of them are likely to be false positives – see Dorothy Bishop’s blog post for a good explanation of the meaning of effect sizes in genetics. Moreover, scientists don’t even know what exactly most of these genes do in our bodies, where they are expressed or what other genes they interact with. We are still a very, very long way from practical, clinical applications.

So why is this company pretending otherwise? What good will it do for a given family to find out that their child has a rare mutation at a single point (or even at multiple points) in these 62 genes? Every single human being, with or without a neurodevelopmental problem, has the odd rare mutation. It takes a lot more than such a tiny blip in our DNA to overthrow the entire brain and create as complex a set of symptoms as are involved in ASD. Telling a family such a thing seems to me to be a little meaningless and unhelpful, until more research is done.

I feel a little bit mollified having scanned through the website of the company who provide this test, as they claim to be not-for-profit and provide families with a package of support involving genetic counselling, which is an important step up from just handing people a genetic test report without any help in interpretation. I think they may be genuinely trying to do something useful and they even appear to be involved in research, which is surely a good sign. I can only assume that some of the other services they offer on their website have a direct benefit to people. I’m just a little worried that there will be other companies who will charge these extortionate amounts of money and just won’t be able deliver anything of actual tangible help or even much in the way of reassurance to families, given the current level of knowledge and understanding on the subject.


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