Heritability of autism spectrum disorders:A meta-analysis of twin studies

BACKGROUND: The etiology of Autism Spectrum Disorder (ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two recent twin studies do not support this and instead re‐affirm strong genetic effects on the liability to ASD, a finding consistent with previous reports. This study conducts a systematic review and meta‐analysis of all twin studies of ASD published to date and explores the etiology along the continuum of a quantitative measure of ASD. METHODS: A PubMed Central, Science Direct, Google Scholar, Web of Knowledge structured search conducted online, to identify all twin studies on ASD published to date. Thirteen primary twin studies were identified, seven were included in the meta‐analysis by meeting Systematic Recruitment criterion; correction for selection and ascertainment strategies, and applied prevalences were assessed for these studies. In addition, a quantile DF extremes analysis was carried out on Childhood Autism Spectrum Test scores measured in a population sample of 6,413 twin pairs including affected twins. RESULTS: The meta‐analysis correlations for monozygotic twins (MZ) were almost perfect at .98 (95% Confidence Interval, .96–.99). The dizygotic (DZ) correlation, however, was .53 (95% CI .44–.60) when ASD prevalence rate was set at 5% (in line with the Broad Phenotype of ASD) and increased to .67 (95% CI .61–.72) when applying a prevalence rate of 1%. The meta‐analytic heritability estimates were substantial: 64–91%. Shared environmental effects became significant as the prevalence rate decreased from 5–1%: 07–35%. The DF analyses show that for the most part, there is no departure from linearity in heritability. CONCLUSIONS: We demonstrate that: (a) ASD is due to strong genetic effects; (b) shared environmental effects become significant as a function of lower prevalence rate; (c) previously reported significant shared environmental influences are likely a statistical artefact of overinclusion of concordant DZ twins

Cross-twin within-trait and cross-trait correlations, stratified by zygosity and gender.

<p>Key points </p><p></p><p>-</p><p>Difficulties in appropriate social interaction are characteristic of both children with autism spectrum disorders and children with callous-unemotional traits.</p><p></p><p>-</p><p>Experimental studies suggest that the nature of atypical social cognition that characterises these two profiles is not identical. However, ‘empathizing’ difficulties have been reported in both groups.</p><p></p><p>-</p><p>Our findings indicate that both social and communication impairments and callous-unemotional traits show modest phenotypic overlap. Aetiological influences accounting for individual differences on each domain were predominantly independent.</p><p></p><p>-</p><p>Although both children with high levels of ASD traits and children with high levels of callous-unemotional traits exhibit difficulties in appropriate social behaviour, the underlying drivers of these impairments are predominantly distinct.</p><p></p><p></p><p></p>-<p>Difficulties in appropriate social interaction are characteristic of both children with autism spectrum disorders and children with callous-unemotional traits.</p>-<p>Experimental studies suggest that the nature of atypical social cognition that characterises these two profiles is not identical. However, ‘empathizing’ difficulties have been reported in both groups.</p>-<p>Our findings indicate that both social and communication impairments and callous-unemotional traits show modest phenotypic overlap. Aetiological influences accounting for individual differences on each domain were predominantly independent.</p>-<p>Although both children with high levels of ASD traits and children with high levels of callous-unemotional traits exhibit difficulties in appropriate social behaviour, the underlying drivers of these impairments are predominantly distinct.</p><p>Cross-trait correlations are below the diagonals; within-trait correlations are on the diagonals. Abbreviations: CU = callous-unemotional; SI = Social interaction; SC = Social communication.</p

Autism Spectrum Disorders and other mental health problems: exploring etiological overlaps and phenotypic causal associations

Objective Recent studies highlight the impact of co-existing mental health problems in autism spectrum disorders (ASD). No twin studies to date reported on individuals meeting diagnostic criteria of ASD. This twin study reports on the aetiological overlap between diagnosis of ASD and emotional symptoms, hyperactivity, and conduct problems measured with the Strengths and Difficulties Questionnaire. Method Genetic and environmental influences on the covariance between ASD and co-existing problems were estimated, in line with the correlated risks model prediction. Phenotypic causality models were also fitted to explore alternative explanations of comorbidity: that co-existing problems are the result of or result in ASD symptoms, that they increase recognition of ASD, or that they arise due to an over-observation bias/confusion when differentiating between phenotypes. Results Over fifty percent of twins with broad spectrum/ASD met the borderline/abnormal levels cut-off criteria for emotional symptoms or hyperactivity, and a quarter met these criteria for the three reported problems. In comparison, between 13%-16% of unaffected twins scored above the cut-offs. The phenotypic correlation between ASD and emotional symptoms was entirely explained by genetic influences and accompanied by a moderate genetic correlation (.42). The opposite was true for the overlap with conduct problems, as non-shared environmental factors had the strongest impact. For hyperactivity, the best-fitting model suggested a unidirectional phenotypic influence of hyperactivity on ASD. Conclusion Our findings suggest a possible effect of hyperactivity on identification of ASD. The lack of genetic influences on conduct problems–ASD overlap further supports the genetic independence of these two phenotypes. Finally, the co-occurrence of emotional symptoms in ASD, compared to other co-occurring problems, is completely explained by common genetic effects