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Study: Father's Age Linked To Mutations In Children

Reykjavik, ICELAND, August 22, 2012 – deCODE Genetics, in collaboration with Illumina, a reported in the journal Nature that a father’s age, not a mother’s, at the time a child is conceived is the single largest contributor to the passing of new hereditary mutations to offspring. The findings come from the largest whole genome sequencing project to examine associations of diseases with rare variants in the genome.
“Strikingly, this study found that a father’s age at the time a child is conceived explains nearly all of the population diversity in new hereditary mutations found in the offspring,” said study lead author Kari Stefansson, M.D., Dr. Med., CEO of deCODE Genetics. “With the results here, it is now clear that demographic transitions that affect the age at which males reproduce can have a considerable impact on the rate of certain diseases linked to new mutation.”
To better understand the cause of new hereditary mutations, the deCODE team sequenced the genomes of 78 Icelandic families with offspring who had a diagnosis of autism or schizophrenia. The team also sequenced the genomes of an additional 1,859 Icelanders, providing a larger comparative population.
On average, the investigators found a two mutation per-year increase in offspring with each one-year increase in age of the father. The average age of the father in the study was 29.7 years old. Also, when specifically examining the genomes of families with autism and schizophrenia, the authors identified in offspring mutations in genes previously implicated in the diseases. They also identified two genes, CUL3 and EPHB2, with mutations in an autism patient subgroup.
“Our results all point to the possibility that as a man ages, the number of hereditary mutations in his sperm increases, and the chance that a child would carry a deleterious mutation that could lead to diseases such as autism and schizophrenia increases proportionally,” said Dr. Stefansson. “It is of interest here that conventional wisdom has been to blame developmental disorders of children on the age of mothers, whereas the only problems that come with advancing age of mothers is a risk of Down syndrome and other rare chromosomal abnormalities. It is the age of fathers that appears to be the real culprit.”
Epidemiological studies in Iceland show the risk of both schizophrenia and autism spectrum disorders increases significantly with father’s age at conception, and that the average age of father’s in Iceland (now 33 years-old) at the time a child is conceived is on the rise. The authors noted that demographic change of this kind and magnitude is not unique to Iceland, and it raises the question of whether the reported increase in autism spectrum disorder diagnosis is at least partially due to an increase in the average age of fathers at conception.

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