Intergenerational Transmission of Quantitative Autism Traits In the General Population and Autism Families

Background:  

Although autism spectrum disorders (ASD) are highly heritable, the genetic background remains largely unclear. Additive genetic effects of risk alleles, each having small effect sizes, have been hypothesized to cause ASD in at least a portion of affected families. Quantitative autism traits (QAT) are continuously distributed and moderately heritable in the general population. Although there is some debate on this matter, unaffected family members of children with ASD possibly show higher levels of QAT than general population controls. This has led to the assumption that QAT in the general population and full ASD might share the same genetic background. To our knowledge, only Constantino and Todd (2005) have ever directly assessed the intergenerational transmission of specific autism traits: children from parents with high levels of QAT appeared to have higher scores on the Social Responsiveness Scale (SRS) compared to children from low scoring parents in the general population.

Objectives:  

1)      To test the hypothesis of intergenerational transmission of QAT in the general population.

2)      To study the intergenerational transmission of QAT in ASD families to affected and unaffected children.

3)      To gain new insights in the genetic mechanisms underlying QAT in both affected and unaffected children.

Methods:  

We collected SRS data on 280 parents-child trios from the general population. From the families participating in studies from Leuven Autism Research, we selected 96 parents-‘child with ASD’ trios and 65 parents-‘unaffected sibling’ trios, excluding children with intellectual disability and including only full siblings and biological parents. Using general linear models, we analyzed the effect of parent SRS scores, the effect of a parent scoring in the highest versus the lowest quartile of SRS scores and the effect of the number of high scoring parents on the SRS total score of the children, for the general population, unaffected siblings and children with ASD separately.

Results:

In the general population trios, the SRS scores of both father and mother had a significant effect on the child’s SRS score. Children of parents with an SRS score in the highest quartile had significantly higher SRS scores compared to children of parents with a lowest quartile SRS score. There was no difference in SRS scores of children with two compared to one high scoring parent, but both groups had higher SRS scores than children with no high scoring parents. Results were very similar in the unaffected siblings in ASD families. However, none of the independent variables had a significant effect on SRS scores of children with ASD.

Conclusions:

The intergenerational transmission of QAT is very similar in the general population and in unaffected siblings of ASD families. However, there seems to be no effect of the QAT of parents on the QAT of children with ASD. These results might indicate that QAT measured in the general population and QAT in unaffected family members of ASD families share the same genetic background, but that in subjects with ASD other genetic or non-genetic factors play an additional or dominant role.