Scientists in Taiwan have used genome sequencing to demonstrate that men who become fathers later in life are more likely to pass on new genetic mutations that increase the risk of schizophrenia in their children.
The study, conducted by researchers at the National Health Research Institutes (NHRI) and National Taiwan University, was published in Molecular Psychiatry in March.
At a news conference yesterday, NHRI vice president Chen Wei-jen (陳為堅) said that while the risks associated with advanced maternal age are well documented, the impact of paternal age on offspring health has received far less attention.
Photo: CNA
NHRI National Center for Geriatrics and Welfare Research assistant researcher Wang Shi-heng (王世亨) said that the team had previously examined correlations between paternal age and schizophrenia using a dataset of more than 7 million Taiwanese medical records.
The study found that children born to fathers aged 25 to 29 had a 0.5 percent lifetime risk of developing schizophrenia, while those whose fathers were 50 or older at the time of birth had a 1 percent risk, Wang said.
The risk increased further if the child’s maternal or paternal grandfather was also of advanced age when the child’s parent was born, he said.
Researchers have proposed two explanations for this pattern — one suggests that men with a higher predisposition to mental illness might be more likely to marry and have children later in life, Wang said.
The second is biological: Because men continue producing sperm throughout their lives, each successive cell division carries a greater chance of replication errors, leading to new genetic mutations that might be passed on to offspring, he said.
The latter explanation is supported by additional evidence, including findings that a higher number of rare mutations correlates with increased schizophrenia risk, and that men pass on about four times as many new genetic mutations to their children as women, he added.
In an effort to prove a causal relationship, the NHRI team conducted whole-genome sequencing on five Taiwanese families, each comprising three siblings diagnosed with schizophrenia and two unaffected parents, he said.
They found that for each additional year a man delayed fatherhood, his child had 1.5 times more new genetic mutations, he said.
A higher number of such mutations was associated with an earlier onset of schizophrenia symptoms in the affected children, he added.
Quantitatively, the study found that about 30 percent of the relationship between paternal age and the age of schizophrenia onset could be explained by age-related mutations, while the remaining 70 percent was likely influenced by familial and environmental factors, Wang said.
Chen said that earlier NHRI research had shown that a paternal age younger than 20 is linked to various other health risks for offspring.
Taken together, these findings highlight the importance of public policies that encourage couples to have children within an optimal age range, he said.
The average age of mothers at childbirth in Taiwan increased from 27.2 in 1991 to 32.4 in 2023, while the average age of fathers rose from 30.3 to 34.6 over the same period, government data showed.
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