What do we know about genes and environmental factors in autism?
Opinions and facts sometimes clash on the question of the causes of autism - genetics or environment? Kristiina Tammimies, associate professor of medical genetics at Karolinska Institutet, has the answer: "Autism is mainly due to the genes we are born with, but environmental factors play a role," she says.
Kristiina Tammimies and her research team at KIND (Center of Neurodevelopmental Disorders at Karolinska Institutet) are conducting leading research on the medical, genetic, and molecular underpinnings of autism and other neurodevelopmental disorders.
"Studies have clearly shown that our genes have a major impact on neurodevelopmental diagnoses such as autism, intellectual disability, and ADHD," says Kristiina Tammimies. "In the case of autism, heritability is estimated at around 80–90 per cent. This doesn’t necessarily mean that the diagnosis is always inherited directly, but rather that a child inherits a genetic predisposition for autism."
Thousands of genes linked to autism
Researchers have identified several thousand genes associated with autism. Many of those genes play crucial roles in early brain development, particularly in the formation of neurons and in communication between nerve cells.
There are both common and rare genetic variations involved. It is estimated that a rare genetic condition is the cause of autism in about 7–20 per cent of cases. In cases of autism accompanied by intellectual disability, rare genetic conditions account for approximately 36–50 per cent of cases.
Many rare genetic conditions, including those connected to autism, are caused bya de novo genetic variant — a new genetic change in the child's DNA that was not inherited from the parents but arose spontaneously in the germ cells. This change can then be passed on to future generations.
"Genes play a very significant role, accounting for up to 90 per cent of autism occurrence in the population, but it remains challenging to pinpoint the exact cause for any given individual," explains Kristiina Tammimies.
Environmental factors as possible cause
Specific environmental factors can affect brain development and contribute to an autism diagnosis. Identified environmental factors include exposure during fetal development to certain medications, viral infections, or environmental toxins and parental age.
However, research has also suggested that genetic components may underlie many of these environmental risk factors. For instance, parental age is positively correlated with the number of de novo genetic variation found in a child. Other environmental risk factors include preterm birth or complications during delivery. It has been clearly demonstrated that vaccinations are not a significant environmental factor in the cause of autism.
"Genes and environment are always intertwined, and it is likely that autism often results from a combination of genetic predisposition and environmental influences," says Kristiina Tammimies. "Continued research into both genetic and environmental factors is essential — we still have much to learn. To fully understand the complexity of autism, it is important to continue investigating how environmental and genetic factors interact, and to promote transdisciplinary research to study these identified factors".
She emphasizes that currently there is no evidence suggesting that environmental factors play a major role in the marked increase in autism diagnoses.
"It is more likely due to a complex interplay of changes in attitudes, awareness, diagnostic criteria, and societal demands," says Kristiina Tammimies.
How genes and the environment work together
In the family shown below, both parents carry certain genetic factors (A and B in the father, and C in the mother) as well as environmental factors (illustrated by green dots) that slightly increase the likelihood of autism. However, the combined influence of these factors is not enough to cross the threshold for autism (represented by the dashed line), and so neither parent is autistic.
Child 1 has inherited a genetic variant with a strong effect (A) and one with a smaller effect (B) from the father, as well as another genetic variant with a small effect (C) from the mother. In addition, Child 1 has a new genetic variant (de novo) with a small effect (D). Together with environmental factors the child has been exposed to, this results in Child 1 reaching the dashed line for autism.
Children 2 and 3 have also inherited genetic variants from their parents (B and C) and have been exposed to environmental factors, but not to an extent sufficient to reach the dashed line for autism.
Child 4 has inherited one genetic variant with a small effect (C) from the mother and also a new (de novo) genetic variant with a strong effect (E). This new variant arose spontaneously, either in the parents' reproductive cells or during early fetal development. Together with certain environmental exposures, this combination is enough for Child 4 to also cross the threshold for autism.
