Autism spectrum disorders (ASD) are highly heritable. Relatives of individuals with ASD can share a part of the symptoms, without developing the full disorder. Autism symptoms are also present in individuals from the general population. Recent research has focused on the presence of quantitative autism traits (QAT) measured by questionnaires in parents and siblings of children with ASD, compared to QAT in the general population. Results are inconclusive however, on whether unaffected relatives have higher levels of QAT or not. This might be due to differences in research populations, since behavioral data as well as molecular genetic research suggest that the genetic etiology of ASD is different in multiplex (MPX) and simplex (SPX) families.
1) To assess if siblings and parents of children with ASD show more QAT than general population controls; and 2) to assess if relatives from MPX families show more QAT than relatives from SPX families.
We compared 117 unaffected siblings (39 boys, 78 girls) with 280 general population control children (100 boys, 180 girls) on the presence of QAT using the Social Responsiveness Scale (SRS), filled out by the parents. 276 parents with at least one child with ASD (132 fathers, 143 mothers) were also compared with 595 adults from the general population (300 men, 295 women), using the adult partner-report version of this questionnaire. Mixed models were constructed to analyze the effect of group (relatives vs. controls) and family type (MPX vs. SPX) on SRS scores, accounting for age, gender and family of origin.
Mean SRS scores for siblings, control children, parents and control adults were 25.4, 26.6, 33.7 and 32.9 respectively, compared to 98.0 and 88.8 for children and adults with ASD. There appeared to be no statistically significant difference in total SRS scores between unaffected siblings and general population control children, nor between mothers of children with ASD and women from the general population. Only fathers of children with ASD expressed higher levels of QAT compared to controls. In neither siblings nor parents we could detect a statistically significant difference in SRS scores between SPX and MPX families.
These results do not support the theory of differential (genetic) etiology in multiplex and simplex families, nor are they in favor of the hypothesis that unaffected relatives (except fathers) express potential genetic risk factors for ASD. We argue that it is important in future studies to give adequate information about the diagnostic status of the relatives that are focus of the research question, since this might explain the inconsistencies between research results. Further genetic and phenotypic research is really needed to elucidate the hypothetical difference between SPX and MPX families, if there is one, and on how to define the difference.
See more of: Clinical Phenotype
See more of: Symptoms, Diagnosis & Phenotype