Advancing parental age and autism: multifactorial pathways

• Both advancing paternal age and maternal age increase the risk of autism in the offspring.
• Different mechanisms likely underlie paternal and maternal age effects.

Converging evidence from epidemiological, genetic, and animal studies supports the hypothesis that advancing parental age, both of the father and mother, increases the risk of autism spectrum disorders (ASD) in offspring. Paternal age has received considerable attention, with whole-genome sequencing studies linking older fathers to higher rates of de novo mutations and increased risk of ASD. The current evidence suggests that the increased risk of ASD in the offspring of older mothers may be related to mechanisms different from those operating in older fathers. Causal pathways probably involve the interaction of multiple risk factors. Although the etiology of ASD is still poorly understood, studies of parental age provide clues into the genetic and environmental mechanisms that mediate the risk of ASD.