Trajectories leading to autism spectrum disorders are affected by paternal age: findings from two nationally representative twin studies.
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.
Lundström
Sebastian
S
Department of Clinical Sciences, Lund University, Malmö, Sweden. sebastian.lundstrom@med.lu.se
Haworth
Claire M A
CM
Carlström
Eva
E
Gillberg
Christopher
C
Mill
Jonathan
J
Råstam
Maria
M
Hultman
Christina M
CM
Ronald
Angelica
A
Anckarsäter
Henrik
H
Plomin
Robert
R
Lichtenstein
Paul
P
Reichenberg
Abraham
A
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