Abstract
BackgroundA number of studies have assessed ages of parents of children with autistic spectrum disorders (ASD), and reported both maternal and paternal age effects. Here we assess relationships with grandparental ages.Methods and FindingsWe compared the parental and grandparental ages of children in the population-based Avon Longitudinal Study of Parents and Children (ALSPAC), according to their scores in regard to 4 autistic trait measures and whether they had been given a diagnosis of ASD. Mean maternal and paternal ages of ASD cases were raised, but this appears to be secondary to a maternal grandmother age effect (P = 0.006): OR = 1.66[95%CI 1.16, 2.37] for each 10-year increase in the grandmother's age at the birth of the mother. Trait measures also revealed an association between the maternal grandmother's age and the major autistic trait–the Coherence Scale (regression coefficient b = 0.142, [95%CI = 0.057, 0.228]P = 0.001). After allowing for confounders the effect size increased to b = 0.217[95%CI 0.125, 0.308](P<0.001) for each 10 year increase in age.ConclusionsAlthough the relationship between maternal grandmother's age and ASD and a major autistic trait was unexpected, there is some biological plausibility, for the maternal side at least, given that the timing of female meiosis I permits direct effects on the grandchild's genome during the grandmother's pregnancy. An alternative explanation is the meiotic mismatch methylation (3 M) hypothesis, presented here for the first time. Nevertheless the findings should be treated as hypothesis generating pending corroborative results from other studies.
Highlights
There is evidence from many parts of the developed world that the prevalence of diagnosed autistic spectrum disorder (ASD) has been rising dramatically
There have been a number of large population based studies of cases of ASD compared either with all births born over the same period or with a set of controls randomly selected from the population at risk
One [2] states that maternal age was significantly associated with autism but that this was secondary to a paternal age effect, whereas the other reports that neither were significant on adjusting for one another [3]
Summary
There is evidence from many parts of the developed world that the prevalence of diagnosed autistic spectrum disorder (ASD) has been rising dramatically. There have been a number of large population based studies of cases of ASD compared either with all births born over the same period or with a set of controls randomly selected from the population at risk. In Western Australia, this problem was circumvented by using a step-wise procedure and offering both maternal and paternal ages [4] Both factors were univariably highly associated with ASD (P,0.001), it was only maternal age that entered the equation with an almost 3-fold increase in risk to children of mothers aged 35+ compared with those ,25.
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