Abstract
BackgroundRecent research has demonstrated that subclinical autistic traits of parents amplify the effects of deleterious mutations in the causation of autism spectrum disorder (ASD) in their offspring. Here, we examined the extent to which two neurodevelopmental traits that are non-specific to ASD—inattention/hyperactivity and motor coordination—might contribute to ASD recurrence in siblings of ASD probands.MethodsData from a quantitative trait study of 114 ASD probands and their brothers, 26% of whom also had ASD, were analyzed. Autistic trait severity was ascertained using the Social Responsiveness Scale-2, attention/hyperactivity problems using the Achenbach System of Empirically Based Assessment, and motor coordination (in a subset of participants) using the Developmental Coordination Disorder Questionnaire.ResultsAmong siblings (affected and unaffected), both categorical recurrence of ASD (Nagelkerke R2 = 0.53) and quantitative ASD trait burden (R2 = 0.55) were predicted by sibling ADHD and motor coordination impairment scores, even though these traits, on average, were not elevated among the unaffected siblings.ConclusionsThese findings in a clinical family cohort confirm observations from general population studies that inattention/hyperactivity and motor impairment—axes of behavioral development that are non-specific to ASD, and often appreciable before ASD is typically diagnosed—jointly account for over 50% of the variation in autistic impairment of siblings, whether ascertained quantitatively or categorically. This finding within a sibling design suggests that background ASD susceptibilities that are inherited but non-specific (“BASINS”) may contribute to additive genetic liability in the same manner that ASD-specific susceptibilities (such as parental subclinical ASD traits and deleterious mutations) engender ASD risk.
Highlights
Recent research has demonstrated that subclinical autistic traits of parents amplify the effects of deleterious mutations in the causation of autism spectrum disorder (ASD) in their offspring
Specificity was studied, showing that affective and oppositional defiant problems were predictive of autistic trait severity, less strong than ADHD problems (Additional file 1: Table S11, online). In this contemporaneous analysis of symptom burden of non-ASD-specific neurodevelopmental traits and ASD recurrence in the siblings of affected probands, we observed that ADHD symptoms and motor coordination impairment jointly accounted for a large share of the variance in both categorical ASD recurrence and quantitative trait severity
These findings in a clinical family cohort confirm observations from general population studies indicating that inattention/hyperactivity and motor coordination impairment—axes of behavioral development that exhibit trait-like stability, have been shown to be correlates of ASD symptomatology [41,42,43,44,45] and which were, on average, normal in the sibling group—account for approximately half of the variation in ASD recurrence, whether ascertained quantitatively or categorically, and controlling for the degree of ASD-specific background genetic liability indexed by the severity of affectation of the proband
Summary
Recent research has demonstrated that subclinical autistic traits of parents amplify the effects of deleterious mutations in the causation of autism spectrum disorder (ASD) in their offspring. Many previous studies have demonstrated the aggregation of non-ASD-specific neurodevelopmental impairments (e.g. motor or attentional impairment) in individuals affected by ASD, even though these inherited neurodevelopmental problems are not included in the DSM5 diagnostic criteria for autism spectrum disorder [6,7,8]. Tempering the notion of causal overlap, a recent genome-wide association study, using large case–control ASD and ADHD samples, did not identify significant overlap in common variant liability [14]. Higher ASD symptom levels have been reported in siblings of children with ADHD [18]
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