Heritability of autism spectrum disorders: a meta‐analysis of twin studies

Abstract

BackgroundThe 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.MethodsA 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.ResultsThe 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.ConclusionsWe 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.

ASD Validity

“…Moreover, heritability studies have variably calculated ASD environmental risk factor influence at 7 to 35 % (Tick et al 2016), 5 to 44 % (Colvert et al 2015), 50 % (Sandin et al 2014), and 55 % (Hallmayer et al 2011). Huguet et al (2016) reviewed ASD findings and proposed a specific distribution of ASD risk factors: 49.8 % common inherited variants, 2.6 % rare inherited CNVs and SNVs, 6.6 % de novo SNVs, 2.9 % de novo CNVs, and 38.1 % environmental risk factors.…”

Protective Effect or Missed Diagnosis? Females with Autism Spectrum Disorder

“…ASD shows higher concordance between monozygotic than dizygotic twins [12], with its heritability estimated to be between 64 -91% [13]. The effect of commonly shared genetic variance has the greatest impact on whether or not an individual develops ASD, with 49% of variance explained by the cumulative effect of multiple mutations found commonly across the general population [14].…”

The Genetic and Epigenetic Basis Involved in the Pathophysiology of ASD: Therapeutic Implications

“…The concordance remarkably from 60 to 92% in monozygotic twins and from 0 to 10% in dizygotic pairs suggests a strong genetic component [41,42]. Nevertheless, the recurrence rate of ADS in siblings of affected children is approximately 2% [43], which is 16 times higher than in the general population but much lower than in single-gene diseases, so the underlying genetic determinants are still largely unknown [41].…”