A variety of genetic factors are likely to be the ultimate cause of most cases of autism. These may work by themselves, or in combination with environmental factors, to lead a child’s brain to develop differently and result in autistic behaviours.
To examine the influences of nature (genetics) and nurture (environment) on a given human quality, scientists study twins.
To appreciate how these studies work, it’s first important to understand there are two types of twins. Identical twins share all of their DNA and, assuming they grow up in the same household, they will also share all of their environment. Fraternal twins also share all of their environment, but only around half of their DNA, just like non-twin siblings.
Twin studies start by defining a clear population, say the metropolitan area of a city, and finding as many sets of twins as possible in that area where one or both of the twins have the given trait of interest – in this case, autism.
Scientists then look at the “concordance” of that trait – that is, the percentage chance that if one twin has autism, the other twin will also have autism. If the concordance is higher for identical twins than fraternal twins, then we can say the difference is due to the increased amount of genetic material shared by the identical twins, and that autism is influenced by genetics.
The first twin study of autism was conducted in 1977 on 11 identical and ten fraternal twins across Great Britain, where at least one of the twins had autism. Concordance for identical twins was 36%, compared to 0% for the fraternal twins.
While the study was only small in size, it provided the first evidence that autism may be genetic in origin. Since this pioneering study, more than a dozen further twin studies have confirmed this original observation.
The best current estimate is that there is a 50-80% concordance for identical twins and a 5-20% concordance for fraternal twins. This indicates a strong genetic component to the condition. The figure for fraternal twins – 5-20% – also represents the chance of a couple who already have a child with autism having a second child with autism (referred to as the “recurrence risk”).
Once scientists have established that the cause of a disorder is influenced by genes, the next task is to identify the exact genes that might be involved. However, after several decades of intensive research, scientists could find no one genetic mutation that all individuals diagnosed with autism shared.
It was these findings (or lack of findings) that led scientists to stop thinking of autism as one condition with one cause. They started viewing it as many different conditions which all have relatively similar behavioural symptoms.
This new view of autism has proved extremely fruitful in discovering subtypes of autism. For example, a number of conditions have very clear genetic or chromosomal abnormalities that can lead to autistic behaviours.
These include disorders that have abnormalities of the chromosomes, such as Down syndrome. While no chromosomal condition itself accounts for any more than 1% of individuals with autism, when combined they account for approximately 10-15% of all individuals diagnosed with autism.
The exact genetic abnormalities that may lead to the remaining cases of autism are not completely clear. There are two reasons for this.
The first is that the genetic regions involved are likely to be very complex. Scientists have needed to develop new techniques to examine them.
The second is that it is probable the genetic mutations are very rare and complex. The DNA chain that forms our chromosomes contains more than 3 billion building blocks. To identify small pieces of DNA that may be linked to the development of autism among so many base pairs, scientists need to study a very large number of people with autism.
To date, no study has been able to examine the thousands of people necessary to identify with accuracy all of the small mutations that might lead to autism.
However, with genetic technologies improving at an astronomical pace, as well as global scientific cooperation that will lead to large numbers of people being studied, major advances in the understanding of the causes of autism are likely in the very near future.
A likely prospect is that many cases of autism will be related to what is called “common genetic variation”. This refers to differences in genes that are also found in many individuals who do not have autism and which by themselves are not sufficient to lead to autism. However, when multiple genetic risk factors are found in the same person, they combine to have a major effect on how the brain develops.
A small proportion of autism cases are also likely to be caused by what are known as de novo (“new”) mutations. Most often, the egg and sperm that create a baby contain genetic material that is present in the mother and father, respectively. However, in rare cases, the egg and sperm may contain genetic material that is not found in either parent. There is now good evidence that some people with autism may have inherited de novo genetic mutations that have an effect on brain development.