Published: 21-03-2013 00:00 | Updated: 12-06-2014 12:58

Older grandfathers pass on autism risk through generations

Men who have children at older ages are more likely to have grandchildren with autism compared to younger grandfathers, according to new research led from Karolinska Institutet. This is the first time that research has shown that risk factors for autism may accumulate over generations.

The study, which is published in the scientific periodical JAMA Psychiatry, is the result of an ongoing collaboration between scientists at Karolinska Institutet, King's College London's Institute of Psychiatry (IoP) in the UK, and the Queensland Brain Institute in Australia. By using Swedish national registers, researchers identified 5,936 individuals with autism and 30,923 healthy controls born in Sweden since 1932. They had complete data on each individual's maternal and paternal grandfathers' age of reproduction and details of any psychiatric diagnosis.

The study found that the risk of autism in the grandchild increased with older paternal age. Men who had a daughter when they were 50 or older were 1.79 times more likely to have a grandchild with autism. Men who had a son when they were 50 or older were 1.67 times more likely to have a grandchild with autism, compared to men who had children when they were 20-24.

Emma Frans, lead author of the study from Karolinska Institutet's Department of Medical Epidemiology and Biostatistics, says: "We know from previous studies that older paternal age is a risk factor for autism. This study goes beyond that and suggests that older grandpaternal age is also a risk factor for autism, suggesting that risk factors for autism can build up through generations."

In Sweden, approximately 1 percent of the population has an autism spectrum disorder (ASD), with the condition affecting more men than women. The condition affects people in very different ways; some are able to live relatively everyday lives, while others will require a lifetime of specialist support. People with ASD have difficulty communicating with and relating to other people, and making sense of the world around them. Recent reports have also suggested that the prevalence of ASD may be increasing.

Autism is known to be caused by a combination of genetic and environmental factors. Previous studies have shown that older paternal age is a risk factor for autism in children. The mechanism behind this link is unknown, but may be explained by mutations occurring in the male sperm cells. Sperm cells divide over time, and on each division the genome is faced by the possibility of new mutations being introduced.

However, most genetic mutations do not result in the child developing autism. The new findings suggest that these 'silent' mutations are passed on to the otherwise healthy child, but may influence the risk of future generations developing autism. The authors suggest that genetic risk could accumulate over generations, or could interact with other risk factors, until it reaches a threshold resulting in the disorder manifesting itself.

The current study was financed by the Swedish Research Council, Karolinska Institutet, and the Swedish Council for Working Life and Social Research (FAS). This press release has to a large extent been published also by the IoP of King's College London.


Autism risk across generations: a population-based study of advancing grandpaternal and paternal age.
Frans E, Sandin S, Reichenberg A, Långström N, Lichtenstein P, McGrath J, et al
JAMA Psychiatry 2013 May;70(5):516-21