Advancing paternal age and autism.
BACKGROUND
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).


METHODS
Historical population-based cohort study.


METHODS
Identification of ASD cases from the Israeli draft board medical registry.


METHODS
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 = 132 271) with data on both paternal and maternal age for the primary analysis and the larger subset (n = 318 506) with data on paternal but not maternal age for sensitivity analyses.


METHODS
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 10 000 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.
Reichenberg
Abraham
A
Department of Psychiatry and Seaver Center for Autism Research, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. avi.reichenberg@mssm.edu
Gross
Raz
R
Weiser
Mark
M
Bresnahan
Michealine
M
Silverman
Jeremy
J
Harlap
Susan
S
Rabinowitz
Jonathan
J
Shulman
Cory
C
Malaspina
Dolores
D
Lubin
Gad
G
Knobler
Haim Y
HY
Davidson
Michael
M
Susser
Ezra
E
D000328:Adult; D001321:Autistic Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics; D006801:Humans; D038801:International Classification of Diseases / Q000706:statistics & numerical data; D007557:Israel / Q000453:epidemiology; D008297:Male; D008423:Maternal Age; D008889:Military Personnel / Q000706:statistics & numerical data; D009154:Mutation / Q000235:genetics; D010331:Paternal Age; D012042:Registries; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012923:Social Class