Paternal age effect

[3] The genetic quality of sperm, as well as its volume and motility, may decrease with age,[5] leading the population geneticist James F. Crow to claim that the "greatest mutational health hazard to the human genome is fertile older males".

[6] The paternal age effect was first proposed implicitly by physician Wilhelm Weinberg in 1912[7] and explicitly by psychiatrist Lionel Penrose in 1955.

Advanced paternal age may be associated with a higher risk for certain single-gene disorders caused by mutations of the FGFR2, FGFR3 and RET genes.

[11] The most significant effect concerns achondroplasia (a form of dwarfism), which might occur in about 1 in 1,875 children fathered by men over 50, compared to 1 in 15,000 in the general population.

[25] A 2017 review concluded that the vast majority of studies supported a relationship between older paternal age and autism and schizophrenia but that there is less convincing and also inconsistent evidence for associations with other psychiatric illnesses.

[3] High paternal age has been suggested as a risk factor for type 1 diabetes,[27] but research findings are inconsistent, and a clear association has not been established.

[24] An editorial accompanying the 2009 paper emphasized the importance of controlling for socioeconomic status in studies of paternal age and intelligence.

[24] On the other hand, later research concluded that previously reported negative associations might be explained by confounding factors, especially parental intelligence and education.

A re-analysis of the 2009 study found that the paternal age effect could be explained by adjusting for maternal education and number of siblings.

[36] A 2013 study of half a million Swedish men adjusted for genetic confounding by comparing brothers and found no association between paternal age and offspring IQ.

[40] The researchers also found a correlation between paternal age and offspring death by injury or poisoning, indicating the need to control for social and behavioral confounding factors.

The authors speculated that this effect may provide a mechanism by which populations have some plasticity in adapting longevity to different social and ecological contexts.

A simulation study concluded that reported paternal age effects on psychiatric disorders in the epidemiological literature are too large to be explained only by mutations.

[43] Older parents also tend to occupy a higher socio-economic position and report feeling more devoted to their children and satisfied with their family.

For example, one study drawing on Finnish census data concluded that increases in offspring mortality with paternal age could be explained completely by parental loss.

[44] On the other hand, a population-based cohort study drawing on 2.6 million records from Sweden found that risk of attention deficit hyperactivity disorder was only positively associated with paternal age when comparing siblings.

[50] During the past two decades evidence has accumulated that pregnancy loss as well as reduced rate of success with assisted reproductive technologies is linked to impaired sperm chromosome integrity and DNA fragmentation.

[46] Improper genomic imprinting and other errors sometimes occur during this process, which can affect the expression of genes related to certain disorders, increasing the offspring's susceptibility.

;[53] Paternal age affects offspring's behavior, possibly via an epigenetic mechanism recruiting a transcriptional repressor REST.

[54] A 2001 review on variation in semen quality and fertility by male age concluded that older men had lower semen volume, lower sperm motility, a decreased percent of normal sperm, as well as decreased pregnancy rates, increased time to pregnancy, and increased infertility at a given point in time.

[65][67][68] The American College of Medical Genetics recommends obstetric ultrasonography at 18–20 weeks gestation in cases of advanced paternal age to evaluate fetal development, but it notes that this procedure "is unlikely to detect many of the conditions of interest."

[69] According to a 2006 review, any adverse effects of advanced paternal age "should be weighed up against potential social advantages for children born to older fathers who are more likely to have progressed in their career and to have achieved financial security.