title: Advancing paternal age and autism.
abstract: 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.
authors.affiliation: 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
authors.forename: Abraham
authors.initials: A
authors.lastname: Reichenberg
authors.forename: Raz
authors.initials: R
authors.lastname: Gross
authors.forename: Mark
authors.initials: M
authors.lastname: Weiser
authors.forename: Michealine
authors.initials: M
authors.lastname: Bresnahan
authors.forename: Jeremy
authors.initials: J
authors.lastname: Silverman
authors.forename: Susan
authors.initials: S
authors.lastname: Harlap
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rabinowitz
authors.forename: Cory
authors.initials: C
authors.lastname: Shulman
authors.forename: Dolores
authors.initials: D
authors.lastname: Malaspina
authors.forename: Gad
authors.initials: G
authors.lastname: Lubin
authors.forename: Haim Y
authors.initials: HY
authors.lastname: Knobler
authors.forename: Michael
authors.initials: M
authors.lastname: Davidson
authors.forename: Ezra
authors.initials: E
authors.lastname: Susser
mesh_terms: 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