Paternal age and intelligence: implications for age-related genomic changes in male germ cells.
A robust association between advancing paternal age and schizophrenia risk is reported, and genetic changes in the germ cells of older men are presumed to underlie the effect. If that is so, then the pathway may include effects on cognition, as those with premorbid schizophrenia are reported to have lower intelligence. There are also substantial genetic influences on intelligence, so de novo genetic events in male germ cells, which accompany advancing paternal age, may plausibly influence offspring intelligence. An association of paternal age with IQ in healthy adolescents may illuminate the mechanisms that link it to schizophrenia. We examined the association of paternal age and IQ scores using the Israeli Army Board data on 44 175 individuals from a richly described birth cohort, along with maternal age and other potential modifiers. A significant inverted U-shaped relationship was observed between paternal age and IQ scores, which was independent from a similar association of IQ scores with maternal age. These relationships were not significantly attenuated by controlling for multiple possible confounding factors, including the other parent's age, parental education, social class, sex and birth order, birth weight and birth complications. Overall, parental age accounted for approximately 2% of the total variance in IQ scores, with later paternal age lowering non-verbal IQ scores more than verbal IQ scores. We found independent effects of maternal and paternal age on offspring IQ scores. The paternal age effect may be explained by de novo mutations or abnormal methylation of paternally imprinted genes, whereas maternal age may affect fetal neurodevelopment through age-related alterations in the in-utero environment. The influence of late paternal age to modify non-verbal IQ may be related to the pathways that increase the risk for schizophrenia in the offspring of older fathers.