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Paternal age effect
The paternal age effect is the statistical relationship between the father's 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. Average paternal age at birth reached a low point between 1960 and 1980 in many countries and has been increasing since then, but has not reached historically unprecedented levels. The rise in paternal age is not seen as a major public health concern.
The genetic quality of sperm, as well as its volume and motility, 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 physician Wilhelm Weinberg in 1912 and explicitly by psychiatrist Lionel 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 several 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 behavioral 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).
Several studies have reported that advanced paternal age is associated with an increased risk of miscarriage. The strength of the association differs between studies. It has been suggested that these miscarriages are caused by chromosome abnormalities in the sperm of aging men. An increased risk for stillbirth has also been suggested for pregnancies fathered by men over 45.
A systematic review published in 2010 concluded that the graph of the risk of low birth weight in infants with paternal age is "saucer-shaped" (U-shaped); that is, the highest risks occur at low and at high paternal ages. Compared with a paternal age of 25–28 years as a reference group, the odds ratio for low birthweight was approximately 1.1 at a paternal age of 20 and approximately 1.2 at a paternal age of 50. There was no association of paternal age with preterm births or with small for gestational age births.
Schizophrenia is associated with advanced paternal age. Some studies examining autism spectrum disorder (ASD) and advanced paternal age have demonstrated an association between the two, although there also appears to be an increase with maternal age.
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Paternal age effect AI simulator
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Paternal age effect
The paternal age effect is the statistical relationship between the father's 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. Average paternal age at birth reached a low point between 1960 and 1980 in many countries and has been increasing since then, but has not reached historically unprecedented levels. The rise in paternal age is not seen as a major public health concern.
The genetic quality of sperm, as well as its volume and motility, 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 physician Wilhelm Weinberg in 1912 and explicitly by psychiatrist Lionel 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 several 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 behavioral 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).
Several studies have reported that advanced paternal age is associated with an increased risk of miscarriage. The strength of the association differs between studies. It has been suggested that these miscarriages are caused by chromosome abnormalities in the sperm of aging men. An increased risk for stillbirth has also been suggested for pregnancies fathered by men over 45.
A systematic review published in 2010 concluded that the graph of the risk of low birth weight in infants with paternal age is "saucer-shaped" (U-shaped); that is, the highest risks occur at low and at high paternal ages. Compared with a paternal age of 25–28 years as a reference group, the odds ratio for low birthweight was approximately 1.1 at a paternal age of 20 and approximately 1.2 at a paternal age of 50. There was no association of paternal age with preterm births or with small for gestational age births.
Schizophrenia is associated with advanced paternal age. Some studies examining autism spectrum disorder (ASD) and advanced paternal age have demonstrated an association between the two, although there also appears to be an increase with maternal age.