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 |
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