Although autism spectrum disorder (ASD) is known to be heritable, patterns of inheritance of sub-clinical autistic traits in non-clinical samples are poorly understood.
To determine the familiality of Social Responsiveness Scale (SRS) scores; we hypothesized that sub-clinical autistic traits would be associated in families.
Design and Setting
Nested case-control study within a population-based longitudinal cohort.
Participants were drawn from the Nurses’ Health Study II (NHS II), a cohort of 116,430 nurses. Cases were index children with reported ASD; controls were frequency matched by years of case births among those not reporting ASD. Of 3161 eligible participants, 2144 returned SRS forms for a child and at least one parent and were included in these analyses.
SRS scores, as reported by nurse participants/mothers and their spouses, were examined in association with liability to ASD using crude and adjusted logistic regression. Child SRS scores were examined in association with parental SRS scores using crude and adjusted linear regression, stratified by case status.
Main Outcome Measure
ASD, assessed by maternal report, validated in a subgroup with the Autism Diagnostic Interview-Revised.
1,649 individuals were included in these analyses, representing 256 ASD cases, 1,393 controls, 1,233 mothers and 1,614 fathers. Index child SRS scores confirmed reported diagnoses. We report for the first time in a large epidemiologic sample that elevated parental quantitative autism traits (QAT) index risk for clinical ASD among offspring. The effect was most pronounced for fathers and for spousal pairs concordant for QAT elevation, which occurred more often than predicted by chance, due to significant preferential mating for QAT. Elevated parent scores significantly increased child scores in controls, corresponding to an increase in approximately 20 points.
Conclusions and Relevance
These findings support the role of additive genetic influences in ASD, underscore the potential role of preferential mating in ASD population genetics, and suggest that typical variation in parental social functioning can produce clinically significant differences in offspring social traits.