New Research Sheds Light on Autism’s Genetic Causes

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A researcher at the Autism Genome Project

Autism remains one of the most poorly understood and troubling developmental disorders of modern medicine. But the genetic revolution could turn that around. Recent research by the groundbreaking Autism Genome Project has identified key mutations and susceptibility genes involved in the disorder. Down the road, this could pave the way for new treatments.

Autism is a poorly understood developmental disorder that can cause impaired social interaction, poor communication skills, repetitive behaviors, and a variety of other symptoms. Cases differ in both the degree of severity and particular symptoms, and include three subtypes along what is called the autism spectrum: Autism, Asperger’s syndrome, and Pervasive Developmental Disorder. Symptoms usually appear before a child is three years old, and the disorder is four times more common in boys than in girls. The National Institute of Health estimates that three to six children in every 1,000 will have some type of autism spectrum disorder.

The cause of autism is notoriously elusive, and has been the focus of extensive research over the past few decades. Because disorders along the autism spectrum are diagnosed behaviorally, they exhibit variable symptoms (thus, the “spectrum”) and aren’t the result of any single cause. Controversies over autism’s causes have debated whether its roots are biological or environmental (see, for example, the debunked vaccine theory). Recent research is showing that like most psychological disorders, autism is linked to a combination of genetic, epigenetic, and environmental factors. However, the emerging consensus is that autism is primarily genetically mediated, with high rates of heritability for both autism (0.7) and Asberger’s syndrome (0.9). Until recently, the actual genetic mutations responsible for autism’s heritability have remained unclear.

Enter the Autism Genome Project (AGP). A large-scale collaborative research project of 120 scientists from 60 different institutions, the AGP aims to identify the genetic architecture involved in susceptibility to autism and spectrum disorders. This month, the AGP reported in Nature its findings that strengthen a growing consensus about the role of genetic mutations called copy number variations (CNVs) in the autism spectrum. Because we all inherit 23 chromosomes from each parent, most folks have two copies of each gene or DNA segment – one from mom, one from dad. A copy number variation is when a particular stretch of base pairs (sometimes encompassing whole genes) differs from the expected number of two. Sometimes a deletion leaves one set, and sometimes a duplication gives three or more sets.

The AGP research found a higher prevalence of CNVs in autistic populations than in controls, which are thought to disrupt genetic mechanisms important for neuronal and intellectual development. Only about 1% of the general population has these CNVs, and they are only present in 3.3% of autism cases. The AGP study also identified four susceptibility genes involved in cellular proliferation, synapse development, and signaling between neurons – but again, mutations on these genes are rare and aren’t common to all individuals with autism. These findings support a growing consensus that autism is caused by a multitude of “rare variants,” none of which directly cause the disorder but which collectively increase an individual’s susceptibility.

AGP started in 2002 and has undergone two major phases of research. Phase One concluded in 2007 and identified two genes involved in autism susceptibility.  Phase Two – the research presented here – compared the genomes of 996 people with autism against those of 1,287 control subjects, including many family studies. Future research at AGP will focus on identifying further CNVs within the population by increasing the sample sizes for comparison.

It’s important to recognize the complexity of factors that lead to autism, as well as our limited understanding of these relationships. Autism is not caused by just a few genes or mutations, and we aren’t going to find a “smoking gun” cause anytime soon. In many ways, autism research exemplifies the growing recognition that genetic determinants are messy and complex (recently covered here at the Hub). Instead of straightforward common genetic causes, the susceptibility to autism is linked to unique combinations of mutations, only some of which show significant overlap between individuals.

This recent AGP research is promising in two ways. First, it opens up new avenues for further research, showing scientists where to look to more clearly understand the causal mechanisms that underlie autism’s genetic component. Second, it paves the way for new treatment options by clarifying which molecular mechanisms are broken in the autistic genome – malfunctions we can develop drugs to counteract. This research is most valuable within the broader context of autism’s epigenetic and environmental factors, and its implications for treatment should be combined with equally important therapy-based approaches.

Autism remains one of the most troubling and elusive psychiatric disorders in the modern age. There is still a great deal we don’t know. Is the disorder becoming more common, or is it being diagnosed more consistently? What environmental factors increase the risk of autism, and how do they interact with genetic components? There are many avenues for further research, and it is promising to see such massively collaborative efforts as the AGP. Slowly, as we shed more light on the autistic genome, we can develop treatments more appropriate to the disorder and the individual patient. And because the costs of genetic testing are dropping rapidly, research should continue to accelerate and put new therapeutic options within reach. Maybe someday, we can look back on this pioneering research as the foundations for a cure.

Check out this short video from ABC covering the recent findings:

[image credit: Autism Genome Project]

Discussion — 18 Responses

  • Dante June 15, 2010 on 4:17 pm

    I’m sorry, but I’m against this; we can confirm the major thinkers and idealists of today ARE on the spectrum, and so am I. I’ve been able to rise above my peers in quite a few fields, if only because I can detect patterns in many forms.

    On the other hand, however, I have met many such people on the Spectrum where they are not aided by their condition, but are worse off for it; I personally think that if such an option became available for adults (IE: those who can make an informed decision about if they should or should not have the treatment) then that’s OK, but ‘treating’ a baby is akin to lobotomy in my book.

  • Dante June 15, 2010 on 12:17 pm

    I’m sorry, but I’m against this; we can confirm the major thinkers and idealists of today ARE on the spectrum, and so am I. I’ve been able to rise above my peers in quite a few fields, if only because I can detect patterns in many forms.

    On the other hand, however, I have met many such people on the Spectrum where they are not aided by their condition, but are worse off for it; I personally think that if such an option became available for adults (IE: those who can make an informed decision about if they should or should not have the treatment) then that’s OK, but ‘treating’ a baby is akin to lobotomy in my book.

  • pjdxxxwa June 15, 2010 on 8:22 pm

    I, also, am against treating babies or small children. As Dante states, many high functioning autism can do well without treatment IF the doctors, parents and SCHOOL PERSONNEL work together to provide a good envirment for the child who learns outside the rote (memorize, memorize, memorize) learning in US public education.

    However, I disagree that the person with autism be the only one to make this decision. Some on the spectrum are unable to see what is best for them or project the future in a realistic light. This is when parents and perhaps two properly educated specialists in autism may be the best ones to decide.

  • pjdxxxwa June 15, 2010 on 4:22 pm

    I, also, am against treating babies or small children. As Dante states, many high functioning autism can do well without treatment IF the doctors, parents and SCHOOL PERSONNEL work together to provide a good envirment for the child who learns outside the rote (memorize, memorize, memorize) learning in US public education.

    However, I disagree that the person with autism be the only one to make this decision. Some on the spectrum are unable to see what is best for them or project the future in a realistic light. This is when parents and perhaps two properly educated specialists in autism may be the best ones to decide.

  • Dante June 15, 2010 on 8:33 pm

    I’m in general agreement there, but I do believe that assigning responsibility to such an individual may be difficult, bordering on impossible. I do remember wishing I was normal, once, before realizing what my gifts enabled me to do.

    Properly educated specialists is another mood point; I consider this a condition with good and bad points, yet I’ve met many such specialists that see it as akin to a disease and wish for it to be treated (hence the Neuro-Diversity movement, which is far more relevant to the Singularity then most people think)

    Perhaps the creation of a ‘self-awareness index’ would help in specifying exactly how capable is the person making their own choices.

    Regardless, I still hold firm about my lobotomy comment.

  • Dante June 15, 2010 on 4:33 pm

    I’m in general agreement there, but I do believe that assigning responsibility to such an individual may be difficult, bordering on impossible. I do remember wishing I was normal, once, before realizing what my gifts enabled me to do.

    Properly educated specialists is another mood point; I consider this a condition with good and bad points, yet I’ve met many such specialists that see it as akin to a disease and wish for it to be treated (hence the Neuro-Diversity movement, which is far more relevant to the Singularity then most people think)

    Perhaps the creation of a ‘self-awareness index’ would help in specifying exactly how capable is the person making their own choices.

    Regardless, I still hold firm about my lobotomy comment.

  • edeyrn June 16, 2010 on 8:19 pm

    you lot are talking about the really soft form of autism………do you know what severe autism is and whats its like having to wash and bathe your 26 year old brother?

  • edeyrn June 16, 2010 on 4:19 pm

    you lot are talking about the really soft form of autism………do you know what severe autism is and whats its like having to wash and bathe your 26 year old brother?

  • Jeremy June 17, 2010 on 2:28 am

    You know, with the controversy that allows arises with discussions of “curing” autism, am I the only one who thinks it would be more useful to “control” it? Find ways to augment the poor social and emotional skills without taking away the various advantages? I don’t know, for some reason I’ve always thought the idea of using technology to create augmented humans with above average intelligence was interesting. This group would then be more capable of creating further intelligence augmentations, and pretty soon you have a basic “intelligence explosion”.

    Not sure if anyone else here is into that kind of thing, but I figured I’d post it. *cough*

  • Jeremy June 16, 2010 on 10:28 pm

    You know, with the controversy that allows arises with discussions of “curing” autism, am I the only one who thinks it would be more useful to “control” it? Find ways to augment the poor social and emotional skills without taking away the various advantages? I don’t know, for some reason I’ve always thought the idea of using technology to create augmented humans with above average intelligence was interesting. This group would then be more capable of creating further intelligence augmentations, and pretty soon you have a basic “intelligence explosion”.

    Not sure if anyone else here is into that kind of thing, but I figured I’d post it. *cough*

  • martin0641 June 17, 2010 on 12:44 pm

    I’m with Jeremy on this one. I liken it to “pretty leprosy” or a Myostatin disorder. We should identify which switches result in increased cognitive ability, and which lead to personal trauma. It is a murky moral ground, and much thought should be given, and people will disagree.

    For millions of years, we have chosen mates in an attempt to give our children the “best” genes available. Once we properly understand our own code, we will be able to give them a basic set of tools to develop into a high-functioning individual while removing defective code (ALS/Sickle Cell/Etc).

    When they are a little older, they can choose how to augment their DNA as they see fit.

  • martin0641 June 17, 2010 on 8:44 am

    I’m with Jeremy on this one. I liken it to “pretty leprosy” or a Myostatin disorder. We should identify which switches result in increased cognitive ability, and which lead to personal trauma. It is a murky moral ground, and much thought should be given, and people will disagree.

    For millions of years, we have chosen mates in an attempt to give our children the “best” genes available. Once we properly understand our own code, we will be able to give them a basic set of tools to develop into a high-functioning individual while removing defective code (ALS/Sickle Cell/Etc).

    When they are a little older, they can choose how to augment their DNA as they see fit.

  • Evan June 22, 2010 on 9:46 am

    Don’t jump to the conclusion that finding a genetic link in a small percentage of Autism cases will lead to a widely applicable treatment.
    This might be possible one day, but for now, most genetic treatments have a very high probability of causing cancer – not a good tradeoff, in my book.

  • Evan June 22, 2010 on 5:46 am

    Don’t jump to the conclusion that finding a genetic link in a small percentage of Autism cases will lead to a widely applicable treatment.
    This might be possible one day, but for now, most genetic treatments have a very high probability of causing cancer – not a good tradeoff, in my book.

  • Pauline July 26, 2010 on 6:53 am

    Dante, I have a 9 year old son on the autistic spectrum. At 3.5 years we were told to leave him behind in an institution and go on with our lives. We refused and he has spent 5.5 years in intensive therapy. He now speaks 2 languages and is starting to read. Leaving babies to grow up and then decide on treatment is ludicrous! Your fine because your on the upper end of the spectrum, think a bit about the rest of the children on the spectrum who might have some resembles of a functional life with treatment!

  • Pauline July 26, 2010 on 2:53 am

    Dante, I have a 9 year old son on the autistic spectrum. At 3.5 years we were told to leave him behind in an institution and go on with our lives. We refused and he has spent 5.5 years in intensive therapy. He now speaks 2 languages and is starting to read. Leaving babies to grow up and then decide on treatment is ludicrous! Your fine because your on the upper end of the spectrum, think a bit about the rest of the children on the spectrum who might have some resembles of a functional life with treatment!