Advanced paternal age

The paternal age effect is the statistical relationship between paternal age at conception and biological effects on the child. Such effects can relate to birthweight, congenital disorders, life expectancy, and psychological outcomes. A 2017 review found that while severe health effects are associated with higher paternal age, the total increase in problems caused by paternal age is low. While paternal age has increased since 1960-1970 this is not seen as a major public health concern.

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

The paternal age effect was first proposed implicitly by Weinberg in 1912, and explicitly by Penrose in 1955. DNA-based research started more recently, in 1998, in the context of paternity testing.

Evidence for a paternal age effect has been proposed for a number of conditions, diseases and other effects. In many of these, the statistical evidence of association is weak, and the association may be related by confounding factors, or behavioural differences. Conditions proposed to show correlation with paternal age include the following:

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. These conditions are Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, achondroplasia, thanatophoric dysplasia, multiple endocrine neoplasia type 2, and multiple endocrine neoplasia type 2b. 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. However, the risk for achondroplasia is still considered clinically negligible. The FGFR genes may be particularly prone to a paternal age effect due to selfish spermatogonial selection, whereby the influence of spermatogonial mutations in older men is enhanced because cells with certain mutations have a selective advantage over other cells (see § DNA mutations).

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