Evidence That Phenotypic Variation In Individuals with ASD Is Associated with Behavior Profiles In Nuclear Family Members

Background: Although autism spectrum disorder (ASD) diagnoses are qualitative, a number of behavioral domains characteristic of the condition can be assessed quantitatively. Two of the most common are a) autistic traits, those behaviors that reflect social impairment, communication impairment, and restricted and repetitive behaviors and interests and b) functional status or adaptive behavior, a measure of limitation in daily activities.  Studies have long suggested that the family members of individuals with ASD (probands) manifest a greater number of autistic traits than expected in the general population. However, the degree to which variation in family traits is related to variation in proband traits is less clear. Similarly, there is little information regarding the expected correlation between the functional status of probands and functional status in their unaffected family members. 

Objectives: To our knowledge, this is the first analysis to investigate the relationship between multi-domain phenotypic variation in probands and behavioral variation in their relatives.  The purpose of this study was to evaluate whether a) autistic traits in parents and unaffected siblings and b) functional status in unaffected siblings are related to proband variation in the same characteristics. 

Methods: This analysis employed data from the Autism Consortium (AC) funded Phenotypic and Genetic Factors in ASD Study, which recruited over 500 families from 5 clinical sites and the community over three years. Autistic traits were measured using the parent Social Responsiveness Scale (SRS) in probands and their siblings; the adult SRS was employed for parents. Functional status was assessed with the Vineland Scales of Adaptive Behavior, administered by a trained clinical interviewer. The association between family members was assessed through bivariate correlations and multiple linear regressions which conditioned on sex and age of the proband.  

Results: The SRS correlations between all family members are shown in Table 1. The significant, positive correlations between parents and probands suggest that parent traits are related to phenotypic severity in offspring with diagnosed ASD. Significant correlations between parents suggest assortative mating. All familial SRS associations remained significant after adjustment for age, sex, and proband functional status. Proband and unaffected sibling functional status were significantly associated (p=0.003). A one unit increase in proband functional status scores predicted a 0.25 point increase in that of their unaffected sibling.    

Conclusions: These preliminary analyses of the AC study phenotyping data provide new insights into ASD familial relationships. Given evidence that autistic traits in family members of probands are related to case severity, family characteristics may be useful in future efforts to identify subgroups of affected individuals. Further, this study suggests that similarity within ASD families is not limited to autistic traits. Siblings of probands with adaptive behavior impairments are more likely to experience functional limitations themselves, suggesting developmental monitoring may be even more warranted in the siblings of individuals with severe ASD. 

Table 1. SRS Total Score Correlations
	Proband	UA Sib	Mom	Dad
Proband	1
UA Sib	n=140, r=0.24 ( p=0.005)	1
Mom	n=203, r=0.15 (p=0.03)	n=115, r=0.32 (p=0.0004)	1
Dad	n=199, r=0.24 (p=0.001)	n=111, r=0.35 (p=0.0002)	n=260, r=0.30 (p<0.0001)	1

See more of: Onset, Clinical Phenotype and Quantitative Traits
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