EBD Blog

Older fathers are more likely to have children who have autism than younger men, according to a study by Abraham Reichenberg and colleagues, writing in the Archives of General Psychiatry. The study, which examined a large number of births in Israel over a 6-year period, revealed that men 40 years or older were nearly 6 times more likely to father autistic children than than men younger than 30. The finding holds even when maternal age is taken into account

According to news reports, there is another interesting twist to this study. The sex ratio differs for the autistic children of older fathers. Whereas the overall ratio is usually about 6:1 (boys:girls), for older fathers the ratio is closer to 1:1.

These results point to a genetic component in autism. With replication and refinement, the nature of the possible genetic component and the extent to which it accounts for autism’s causes will become clearer. Is it a true lead? With what does it interact? What accounts for autism among children born of younger fathers?

Advancing Paternal Age and Autism

Abraham Reichenberg, PhD; Raz Gross, MD, MPH; Mark Weiser, MD; Michealine Bresnahan, PhD; Jeremy Silverman, PhD; Susan Harlap, MBBS; Jonathan Rabinowitz, PhD; Cory Shulman, PhD; Dolores Malaspina, MD; Gad Lubin, MD; Haim Y. Knobler, MD; Michael Davidson, MD; Ezra Susser, MD, DrPH

Arch Gen Psychiatry.2006;63:1026-1032.

Context Maternal and paternal ages are associated with neurodevelopmental disorders.

Objective To examine the relationship between advancing paternal age at birth of offspring and their risk of autism spectrum disorder (ASD).

Design Historical population-based cohort study.
Setting Identification of ASD cases from the Israeli draft board medical registry.

Participants We conducted a study of Jewish persons born in Israel during 6 consecutive years. Virtually all men and about three quarters of women in this cohort underwent draft board assessment at age 17 years. Paternal age at birth was obtained for most of the cohort; maternal age was obtained for a smaller subset. We used the smaller subset (n=132271) with data on both paternal and maternal age for the primary analysis and the larger subset (n=318506) with data on paternal but not maternal age for sensitivity analyses.

Main Outcome Measures Information on persons coded as having International Classification of Diseases, 10th Revision ASD was obtained from the registry. The registry identified 110 cases of ASD (incidence, 8.3 cases per 10000 persons), mainly autism, in the smaller subset with complete parental age data.
Results There was a significant monotonic association between advancing paternal age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P< .001) more likely to have ASD compared with offspring of men younger than 30 years, after controlling for year of birth, socioeconomic status, and maternal age. Advancing maternal age showed no association with ASD after adjusting for paternal age. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on maternal age.

Conclusions Advanced paternal age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing age or alterations in genetic imprinting.

Link to the abstract, to coverage by Thomas Maugh of the Los Angeles Times, to coverage by the BBC, and to related coverage via Google.