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An older father increases risk of autism and schizophrenia

Robin Wulffson MD's picture
schizophrenia, autism, paternal age, mutations, birth defects

A new study has reported that the age at which a father sires children determines how many mutations those offspring inherit. Therefore, men who postponed starting a family in the their thirties, forties, and beyond could be increasing the chances that their children will develop autism, schizophrenia, and other diseases often linked to new mutations. The results were published on August 22 in the journal Nature.

“The older we are as fathers, the more likely we will pass on our mutations,” notes lead author Kári Stefánsson, chief executive of deCODE Genetics in Reykjavik. He added, “The more mutations we pass on, the more likely that one of them is going to be deleterious.” His company maintains genetic information on most Icelanders

Stefánsson and his team compared the whole-genome sequences of 78 trios of a mother, father and child. They searched for mutations in the child that were not present in either parent and that must therefore have arisen spontaneously in the egg, sperm, or embryo. The researchers note that their study is the largest such study of nuclear families to date. Previous studies of new mutations through direct examination of parent-offspring transmission were largely limited to studying specific genes or regions.

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Because women are born with a finite number of eggs, they are capable of passing on only about 14 new mutations to their offspring throughout their lifetime. In contrast, men are capable of forming new mutations each time they generate sperm. The researchers found that fathers passed on nearly four times as many new mutations as mothers (fathers: 55 average; mothers: 14 average). The father’s age also accounted for nearly all of the variation in the number of new mutations in a child’s genome, with the number of new mutations being passed on rising exponentially with paternal age. The researchers estimated that a 36-year-old will pass on twice as many mutations to his child as a man of 20, and a 70-year-old eight times as many. In addition, they estimate that an Icelandic child born in 2011 will harbor 70 new mutations, compared with 60 for a child born in 1980; the average age of fatherhood rose from 28 to 33 over that time.

The researchers note that on the average, men form an additional two new mutations with each additional year of age at the time of conception of the child; furthermore, every 16.5 years, there is a doubling of new mutations in their sperm.

Reference: Nature

See also: The health benefits of having an older dad