The cause of autism is not completely understood, but several risk factors have been identified that are associated with its occurrence, including advanced age of both mothers and fathers. Now, a new study reveals that advanced age of grandparents may also predispose children to autism.

The study, published in JAMA Psychiatry, evaluated multiple generations of people born in Sweden since 1932. The researchers obtained parental age and grandparental age at the time of birth for nearly 6000 children with a diagnosis of autism and an additional 31,000 control cases. A significant association was found between older grandfathers and childhood autism. Men who fathered a daughter after the age of 50 were 1.79 times more likely to have a grandchild with autism, compared with men who fathered a child between the ages of 20 and 24. Men who fathered a son after the age of 50 were 1.67 times more likely to have a grandchild with autism.

The authors concluded that the risk of autism may develop over generations, owing to genetic mutations or alterations in male sperm cells that are passed on to offspring. Possibly, these alterations remain silent in the first generation of offspring, but will get passed on to future generations where they interact with other risk factors or environmental conditions until a disorder manifests itself.

Several studies have reported the link between advanced parental age and autism in children, but this is among the first to link grandfathers with a risk of autism. Men who fathered children after the age of 50 were 2.2 times more likely to have a child with autism, according to an analysis by some of the same researchers as the grandparental age study. Similarly, mothers who had children after the age of 35 were 1.31 times more likely to have a child with autism. A separate study reported that the risk of autism increased significantly with every 10-year increase in maternal and paternal age.

Advanced age of fathers and grandfathers has also been linked to other psychiatric diagnoses. For example, the risk of schizophrenia for offspring doubles when a man fathers a child after the age of 55. Children of maternal grandfathers who fathered children after the age of 55 have a 2.79-fold risk of schizophrenia.

The current study highlights the complex nature of autism and how it develops. The increased risk of autism identified by this group is still small, but it suggests that fathers’ and grandfathers’ lifestyle and reproductive choices can affect future progeny. Of course, many factors affect the health of a genome, and simply having old parents or grandparents should not be the only factor that limits the decision to have children. But, findings such as these remind us that the circle of life is not a perfect, unbroken system. The genome is a living, changing entity that evolves and adapts to environmental conditions, disease, and lifestyle exposures to affect, if not our own future, the future of our descendants.

References

Croen LA, Najjar DV, Fireman B, & Grether JK (2007). Maternal and paternal age and risk of autism spectrum disorders. Archives of pediatrics & adolescent medicine, 161 (4), 334-40 PMID: 17404129

Frans EM, McGrath JJ, Sandin S, Lichtenstein P, Reichenberg A, Långström N, & Hultman CM (2011). Advanced paternal and grandpaternal age and schizophrenia: a three-generation perspective. Schizophrenia research, 133 (1-3), 120-4 PMID: 22000939

Frans EM, Sandin S, Reichenberg A, Långström N, Lichtenstein P, McGrath JJ, & Hultman CM (2013). Autism risk across generations: a population-based study of advancing grandpaternal and paternal age. JAMA psychiatry (Chicago, Ill.), 70 (5), 516-21 PMID: 23553111

Hultman CM, Sandin S, Levine SZ, Lichtenstein P, & Reichenberg A (2011). Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies. Molecular psychiatry, 16 (12), 1203-12 PMID: 21116277

Sandin S, Hultman CM, Kolevzon A, Gross R, MacCabe JH, & Reichenberg A (2012). Advancing maternal age is associated with increasing risk for autism: a review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 51 (5), 477-4860 PMID: 22525954

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