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Examining the Broader Autism Phenotype in the Context of Genetic Etiology
Considering the phenotypic heterogeneity within autism spectrum disorder (ASD), children’s individual differences may relate to subclinical parental traits associated with ASD symptoms and social impairment, known as the broader autism phenotype (BAP; Bolton et al., 1994). However, the extent by which parents’ genetic contributions interact with BAP contributions is unclear. One hypothesis is that parents with an ASD-associated genetic event (e.g., disruptive single gene mutation, rare copy number variations) will present with an elevated rate of BAP and other social problems, and their child’s ASD symptoms will be more severe.
Objectives:
We examined the extent to which parental BAP is associated with children’s genetic etiology, specifically as it pertains to rare inherited genetic events relative to children with other disruptive de novo genetic events.
Methods:
Local participants (N = 105) were parents of a child with an ASD diagnosis who completed either the Simons Simplex Collection (n = 77) and/or a genetics-first study (“TIGER”, n = 28) in which a parental phenotyping battery included three measures related to ASD symptoms of social impairment (see Table 1). Parents were grouped based upon their child’s genetic etiology. Given the aim of investigating clinical observations of BAP, we focused on the Broader Phenotype Autism Symptom Scale (BPASS, Dawson et al., 2007), a clinical interview capturing social motivation and flexibility, as well as nonverbal social behaviors such at expressiveness and conversational skills. ANOVAs tested group differences (Tukey correction for planned comparisons). Pearson correlations tested for BAP parent-child associations with critical ASD symptoms.
Results:
There were no group differences in age, full-scale IQ, BPASS total, or BAPQ total, p’s > .62. Regarding clinical observations, all parents were observed within the normal range in expressiveness and conversational skills, with good to moderate facial expressions. Group differences indicated that the De Novo group exhibited elevated problems with sociability in groups, F(2,82) = 3.22, p = .045, relative to the Inherited group. Low or abnormal parents’ group sociability was related to similar problems in probands’ social and adaptive abilities (see Figure 1), as noted by SRS-II subdomains, VABS-III composite, and VABS-III subdomains, but not the SRS-II overall t-score. Of note, the De Novo group exhibited weaker associations between parental BAP and proband ASD symptomology relative to the Inherited group (e.g., VABS-II composite: De Novo r = -.11, Inherited r = -.21).
Conclusions:
Contrary to hypotheses, parents in the Inherited group that share a rare ASD-risk genetic event with their child did not exhibit elevated BAP symptoms. Yet, parental sociability in groups was associated with proband ASD symptomology to a greater extent for Inherited relative to De Novo parents, aligned with our initial prediction of more severe ASD symptoms for children whose parents have both BAP symptoms and are the source of that child’s genetic etiology. A better understanding of the severity of specific genetic events (Woodbury-Smith, et al., 2018) combined with this work in understanding individual BAP differences may elucidate appropriate identification and treatment options (Gerdts et al., 2013).