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Having Older Grandfather May Raise Child's Autism Risk: Study

By E.J. Mundell
HealthDay Reporter

WEDNESDAY, March 20 (HealthDay News) -- The odds that a child will develop autism could be linked to their grandfather's age at the time they were born, a new Swedish study suggests.

The study found that men who fathered a child at the age of 50 or older were more likely to have a grandchild with autism, suggesting that the risk might be passed down through successive generations.

Men who had a daughter at age 50 or older were 79 percent more likely to have a grandchild with autism compared to men who fathered when they were in their early 20s, the research team reported in the March 20 issue of the journal JAMA Psychiatry. Men who fathered a son at age 50 or older had a 67 percent higher risk of having a grandchild with the disorder compared to men who fathered a child as young adults.

"We tend to think in terms of the here and now when we talk about the effect of the environment on our genome," said study co-author Dr. Avi Reichenberg, who worked on the study while at King's College London's Institute of Psychiatry, in England. "For the first time in psychiatry, we show that your father's and grandfather's lifestyle choices can affect you.

"This doesn't mean that you shouldn't have children if your father was old when he had you, because while the risk is increased, it is still small," added Reichenberg, who is now an autism researcher at the Icahn School of Medicine at Mount Sinai, in New York City. "However, the findings are important in understanding the complex way in which autism develops."

Although the study found a correlation between advanced age in grandfathers and the odds for autism in children, it is only an observational trial, so it cannot prove cause and effect. And another expert also stressed that the absolute risk to any one family remains small.

"Although there was a statistically significant increase in the incidence of autism in families with older grandparents, it must be remembered that autism was still extremely infrequent even in families with the oldest grandparents," said Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at Steven & Alexandra Cohen Children's Medical Center of New York, in New Hyde Park. "Thus, older parents and grandparents should not be unduly worried."

The new research was published on the same day that the U.S. Centers for Disease Control and Prevention announced that one in every 50 U.S. school children now has an autism spectrum disorder -- up from the 2007 estimate of 1 in 88. The CDC says improved detection and diagnosis are probably responsible for most of that increase.

In the new study, researchers looked at data from Sweden's national registries and compared about 6,000 people with autism to about 31,000 people without the condition. They looked at the age of each person's maternal and paternal grandfather at the time of the individual's birth.

The link between autism and a grandfather's age was significant, the team said, and pointed to the genetic underpinnings of the condition. They noted that previous studies have found a link between older fathers and rising odds for autism in their children, such that men who have a child when age 50 or older have a double the risk of having a child with the disorder.

Mutations lying within sperm cells might be the culprit, the researchers said. Sperm cells undergo division throughout the lifespan, and with each new division errors in the genome can occur. Some of these mutations might remain "silent" in a man's child but then accumulate or re-emerge to cause problems in future generations.

"These findings add further support to the belief that subtle genetic abnormalities -- defects that were previously undetectable -- are likely responsible for some cases of autism," Adesman said.

This type of research might lead to tests that could pinpoint a child's odds for an autism spectrum disorder, he added. "Newer molecular genetic laboratory tests will increasingly allow scientists and doctors to find atypical parts of chromosomes that put a child at increased risk for an autism spectrum disorder," Adesman said.

Another expert said the new study could raise as many questions as it answers.

Although the researchers offer theories as to how a man's age might affect the risk for autism in his descendants, "more research is needed to better understand how this occurs," said Alycia Halladay, senior director for environmental and clinical sciences at the advocacy group Autism Speaks. "For example, it could be through modifications of DNA, or it could result from environmental factors modifying how DNA is expressed," she said.

"This study is important because it utilizes rich datasets with health record information," Halladay added. "This approach can open the door for future work on genetic and environmental factors associated with [autism spectrum disorders]."

More information

Find out more about autism spectrum disorders at the American Psychiatric Association.

SOURCES: Andrew Adesman, M.D., chief, developmental & behavioral pediatrics, Steven & Alexandra Cohen Children's Medical Center of New York, New Hyde Park; Abraham Reichenberg, M.D., Ph.D., fellow, Seaver Center for Autism Research and Treatment, Icahn School of Medicine at Mount Sinai, New York City; Alycia Halladay, Ph.D., senior director, Environmental and Clinical Sciences, Autism Speaks; March 20, 2013, JAMA Psychiatry

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