On the Nature of Monozygotic Twin Concordance and Discordance for Autistic Trait Severity: A Quantitative Analysis.

The characterizing features of autism spectrum disorder (ASD) are continuously distributed in nature; however, prior twin studies have not systematically incorporated this knowledge into estimations of concordance and discordance. We conducted a quantitative analysis of twin–twin similarity for autistic trait severity in three existing data sets involving 366 pairs of uniformly-phenotyped monozygotic (MZ) twins with and without ASD. Probandwise concordance for ASD was 96%; however, MZ trait correlations differed markedly for pairs with ASD trait burden below versus above the threshold for clinical diagnosis, with R2s on the order of 0.6 versus 0.1, respectively. Categorical MZ twin discordance for ASD diagnosis is rare and more appropriately operationalized by standardized quantification of twin–twin differences. Here we provide new evidence that although ASD itself is highly heritable, variation-in-severity of symptomatology above the diagnostic threshold is substantially influenced, in contrast, by non-shared environmental factors which may identify novel targets of early ASD amelioration.