title: Trajectories leading to autism spectrum disorders are affected by paternal age: findings from two nationally representative twin studies.
abstract: BACKGROUND
  Despite extensive efforts, the causes of autism remain unknown. Advancing paternal age has been associated with various neurodevelopmental disorders. We aim to investigate three unresolved questions: (a) What is the association between paternal age and autism spectrum disorders (ASD)?; (b) Does paternal age moderate the genetic and environmental etiological factors for ASD? (c) Does paternal age affect normal variation in autistic-like traits?
  
  
  METHODS
  Two nationally representative twin studies from Sweden (n = 11, 122, assessed at age 9 or 12) and the UK (n = 13, 524, assessed at age 9) were used. Categorical and continuous measures of ASD, autistic-like traits and autistic similarity were calculated and compared over paternal age categories.
  
  
  RESULTS
  Both cohorts showed a strong association between paternal age and the risk for ASD. A U-shaped risk association could be discerned since the offspring of both the youngest and oldest fathers showed an elevation in the risk for ASD. Autistic similarity increased with advancing paternal age in both monozygotic and dizygotic twins. Both cohorts showed significantly higher autistic-like traits in the offspring of the youngest and oldest fathers.
  
  
  CONCLUSIONS
  Phenomena associated with paternal age are clearly involved in the trajectories leading to autistic-like traits and ASD. Mechanisms influencing the trajectories might differ between older and younger fathers. Molecular genetic studies are now needed in order to further understand the association between paternal age and ASD, as well as normal variation in social, language, and repetitive behaviors in the general population.
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden. sebastian.lundstrom@med.lu.se
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lundström
authors.forename: Claire M A
authors.initials: CM
authors.lastname: Haworth
authors.forename: Eva
authors.initials: E
authors.lastname: Carlström
authors.forename: Christopher
authors.initials: C
authors.lastname: Gillberg
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mill
authors.forename: Maria
authors.initials: M
authors.lastname: Råstam
authors.forename: Christina M
authors.initials: CM
authors.lastname: Hultman
authors.forename: Angelica
authors.initials: A
authors.lastname: Ronald
authors.forename: Henrik
authors.initials: H
authors.lastname: Anckarsäter
authors.forename: Robert
authors.initials: R
authors.lastname: Plomin
authors.forename: Paul
authors.initials: P
authors.lastname: Lichtenstein
authors.forename: Abraham
authors.initials: A
authors.lastname: Reichenberg
mesh_terms: D015984:Causality; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology* / Q000235:genetics* / Q000523:psychology; D015331:Cohort Studies; D004200:Diseases in Twins / Q000453:epidemiology* / Q000235:genetics* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D010331:Paternal Age; D012931:Social Environment; D013548:Sweden; D006113:United Kingdom