For quite some time now, there has been strong evidence that the age of the father has a significant effect on the chance of his child having autism.1 There has been evidence that the mother’s age also plays a role, but its effect is much smaller.2 However, these studies simply demonstrate a correlation between parental age and autism. They do not show that increased parental age plays a direct role in the cause of autism. However, a recent study published in the journal Nature has changed that. It seems to provide a direct link between the age of the father and autism in the child.
The authors of the study examined the entire genomes of 78 parent-offspring trios (mother, father, and child) to directly determine what mutations the child received from the father’s sperm cell and what mutations the child received from the mother’s egg cell. Because they were specifically interested in the cause of neurological disorders, they used a large number of trios that contained a child with either autism or schizophrenia. In the end, 44 of the children had autism spectrum disorder, and 21 were schizophrenic. In addition, the genomes of 1,859 other people were sequenced to serve as a population comparison.
The authors focused on the de novo mutations in the children. These are mutations that do not exist in either parent but do exist in the child. Thus, they must arise from a mutation that occurred when the father made his sperm or the mother made her egg. Such mutations happen in every production of egg and sperm cells, and the authors wanted to know which parent (if either) was more responsible for them. The results were surprising, to say the least!
When they looked at de novo mutations in the children’s genomes, they found that the vast majority of the child’s mutations could be accounted for by the father’s sperm.3 The mother’s egg passed on some mutations, but not nearly as many as the father’s sperm. In the end, they found that the father transmitted almost nine times as many de novo mutations as the mother. They further found that the number of mutations transmitted by the father’s sperm increases linearly with his age! As the authors state:
Seeing an association between father’s age and mutation rate is not surprising, but the large linear effect of more than two extra mutations per year, or the estimated exponential effect of paternal mutations doubling every 16.5 years, is striking.
So for every year a man waits to have a child, he will pass on two extra de novo mutations to his child. The authors go on to note that the average age of fathers has increased over time in the country where the study was done (Iceland). They then say:
Demographic change of this kind and magnitude is not unique to Iceland, and it raises the question of whether the reported increase in ASD diagnosis lately is at least partially due to an increase in the average age of fathers at conception.
In the end, then, I think the authors have made a good case for a direct link between a father’s age and the risk for his child to develop autism. Is this the only factor involved in autism? Almost certainly not. However, it can explain at least some of the increase we are seeing in autism rates.
1. Abraham Reichenberg, et al., “Advancing Paternal Age and Autism,” Arch Gen Psychiatry, 63:1026–1032, 2006
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2. Lisa A. Croen, et al., “Maternal and Paternal Age and Risk of Autism Spectrum Disorders,” Arch Pediatr Adolesc Med, 161:334-340, 2007.
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3. Augustine Kong, et al., “Rate of de novo mutations and the importance of father’s age to disease risk,” Nature, 488:471-475, 2012.
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