Autism spectrum disorder (ASD) refers to a range of neurodevelopmental disorders characterized by challenges with social skills, speech and nonverbal communication, and repetitive behaviors. ASD includes autism as well as Asperger syndrome and pervasive developmental disorder-not otherwise specified (PDD-NOS). The causes of ASD are still not fully understood, but research suggests that both genetics and environmental factors play important roles.
When it comes to genetics, ASD is considered a complex disorder meaning that there are likely multiple genes involved, rather than just one. In most cases, ASD is not caused by a single genetic mutation but rather by variations in many genes that each contribute to the risk. There is also evidence that epigenetic factors, or changes that affect how genes are expressed, may be involved.
Given the complex genetic nature of ASD, determining exactly which parent it comes from is complicated. However, research has uncovered some patterns in terms of which parents are more likely to pass on genetic risk factors. Below is an overview of what we know so far about the genetic contributors to ASD from each parent.
Genetic Factors from Fathers
Several studies have found that fathers, particularly older fathers, are more likely to pass on genetic mutations that increase the risk for ASD. Some key research findings on paternal factors include:
– Older fathers have a higher chance of passing on spontaneous genetic mutations. As men age, their sperm undergoes more replications and is more likely to develop de novo mutations that were not inherited from either parent. These spontaneous mutations become more common with increasing paternal age.
– Children of men over 50 were 1.79 times more likely to have ASD compared to children of men under 30 years old, in a study of over 5 million children. The risk increased steadily with paternal age.
– Rare spontaneous mutations called copy number variants (CNVs) are more common in the sperm of older men. These CNVs disrupt genes in various ways and have been linked to increased ASD risk.
– A specific mutation in the MECP2 gene associated with autism is almost always inherited from the father. The mutation is also linked to increased ASD recurrence in siblings.
– Exposure to pesticides has been associated with higher rates of autism in children. Pesticides may cause genetic changes in sperm.
– Fathers who have traits linked to the broader autism phenotype (BAP), like aloof personality or pragmatic language deficits, are more likely to have children with ASD even when the mother does not have those traits.
Overall, advanced paternal age and related genetic factors play an important role in passing on genetic risk for ASD. Fathers contribute somewhere between 30-50% of the genetic risk.
Genetic Factors from Mothers
Research also supports maternal genetic contributions to ASD risk, though they may be smaller on average than paternal factors. Some key findings on mothers include:
– Maternal inheritance accounts for approximately 15% of ASD risk according to a large Swedish population study.
– Mothers with mutations in genes involved in brain development and function have an increased chance of having children with ASD. Examples include mutations in PTEN, CHD8, and FOXP1.
– Mothers who carry deletions and duplications of DNA called copy number variants (CNVs) can pass them on to children. Several of these CNVs are linked to autism.
– Mothers with autoimmune diseases like rheumatoid arthritis and celiac disease are more likely to have a child with ASD, suggesting immune system genes may be inherited.
– Women with family members who have ASD have a higher recurrence risk of having an affected child. However, the mechanism is unclear and may involve genetics, the prenatal environment, or both.
– Like fathers, advancing maternal age also increases ASD risk, though to a lesser degree. The risk steadily increases after age 30.
Overall, mothers clearly contribute genetic risk factors for ASD as well. However, evidence suggests paternal factors play a larger role, on average.
Interplay Between Maternal and Paternal Genes
While fathers and mothers both contribute genetic risk for ASD, their genes don’t act independently. Rather, some combinations of maternal and paternal genes appear to interact to increase risk. For example:
– Inheriting a high-risk gene from both parents is more damaging than inheriting it from just one. The effects are additive.
– Parents who are healthy carriers of a genetic mutation can have a child with ASD if the child inherits two bad copies, one from each parent.
– Certain combinations of common genetic variants increase risk more than having either variant alone. This epistasis suggests complex gene-gene interactions.
– Imprinting defects can lead to ASD when key genes are silenced or activated based on parental origin. For example, a maternally-inherited deletion in chromosome 15q11-13 is linked to ASD risk.
– Assortative mating may play a role. Parents who both have traits linked to the broader autism phenotype, like aloof personality, may pass on more ASD genes.
Overall, the interplay between maternal and paternal genetic contributions is complex and important for fully understanding ASD inheritance patterns.
Environmental Factors
Genetics are not destiny for ASD. Environmental influences in the womb and early life also affect whether someone develops the disorder. Some key findings on environmental risks include:
– Advanced parental age increases spontaneous mutations in sperm and eggs, adding to genetic risk
– Exposure to air pollution and pesticides during pregnancy increases ASD risk
– Having an infection that leads to an immune response during pregnancy raises risk
– Extreme prematurity and very low birth weight raise risk for ASD
– Fetal exposure to the medications valproic acid and thalidomide is linked to higher ASD rates
– Poor maternal nutrition and metabolic conditions like diabetes and obesity during pregnancy may contribute
– Lack of folate and vitamin D prenatally have been implicated though results are mixed
In many cases, environmental factors likely interact with genetic susceptibilities to trigger ASD. Both parental contributions and the prenatal environment play important interacting roles in the development of autism spectrum disorder.
Recurrence Rates for Siblings
Looking at rates of ASD recurrence among siblings provides some additional insight into how maternal and paternal genes combine to determine risk. Some key patterns include:
– When one child has ASD, the risk of a subsequent sibling also developing ASD goes up sharply, to around 12-20% compared to around 1% in the general population.
– However, most siblings do not develop ASD, highlighting the importance of non-shared environmental and genetic factors even within families.
– Brothers of women with ASD have a higher chance of having a child with ASD compared to sisters, suggesting male family members carry a higher genetic load.
– Families with more than one affected child tend to have more copy number variants (CNVs). These families may carry certain high-risk CNVs that get passed to multiple children.
– In identical twins where one child has ASD, if the affected twin is female the chances the other twin has ASD may be up to 95%. If the affected twin is male, the concordance rate drops to around 25%. This suggests some X-linked genetic factors.
– When couples who already have one child with ASD conceive again, the recurrence risk is around 18.7% overall. It is higher when the father rather than mother has the broader autism phenotype.
Looking at patterns of recurrence provides clues about how paternal, maternal, and random genetic factors combine together to contribute to ASD risk within families.
Conclusions
In summary, autism spectrum disorder is complex at the genetic level, involving many different genes and mutations that can come from both parents. However, research suggests fathers contribute a larger portion, on average, of the genetic risk. Specific genetic factors that are more likely to come from dads include spontaneous mutations in sperm, especially in older fathers, as well as inherited copy number variants and mutations in genes like MECP2. Mothers also clearly contribute genetic risk, including through inherited autism-linked mutations, copy number variants, and immune system genes. The interplay between maternal and paternal genes can further heighten risk when certain combinations are present. Beyond genetics, environmental influences before and after birth modify risk, so autism spectrum disorder depends on both nature and nurture. While our understanding of ASD inheritance continues to evolve, it is clear that paternal, maternal, and environmental influences all play important interacting roles.