Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul;50(4):263-272.
doi: 10.1007/s10519-019-09987-2. Epub 2019 Dec 18.

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

Lauren Castelbaum  1 , Chad M Sylvester  1 , Yi Zhang  1 , Qiongru Yu  1 , John N Constantino  2   3
Affiliations

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

Lauren Castelbaum et al. Behav Genet. 2020 Jul.

Abstract

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.

Keywords: Autism; Development; Epidemiology; Epigenetics; Genetics; Heritability; Twin studies.

PubMed Disclaimer

Conflict of interest statement

Dr. Constantino receives royalties from Western Psychological Services for the commercial distribution of the Social Responsiveness Scale, a quantitative measure of autistic traits for ages 30 months through adulthood. Lauren Castelbaum, Chad M. Sylvester, Yi Zhang and Qiongru Yu declare that they have no biomedical financial interests or potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Distributions of MZ twin-co-twin differences for autistic trait severity in superimposed density plots for the three respective samples in the study
Fig. 2
Fig. 2
Scatter plots of MZ twin-co-twin data: a General population, Social Responsiveness Scale (SRS) scores; b Clinically-ascertained MZ twins, SRS; c Clinically-ascertained MZ twins, Autism Diagnostic Observation Scale (ADOS)
Fig. 3
Fig. 3
Distribution of clinical MZ twin–twin SRS scores in relation to an established cutoff for clinical-level affectation
See this image and copyright information in PMC

References

    1. Anagnostou E, Jones N, Huerta M, Halladay AK, Wang P, Scahill L, Horrigan JP, Kasari C, Lord C, Choi D, Sullivan K, Dawson G. Measuring social communication behaviors as a treatment endpoint in individuals with autism spectrum disorder. Autism. 2015;19(5):622–636. - PubMed
    1. Colvert E, Tick B, McEwen F, Stewart C, Curran SR, Woodhouse E, Gillan N, Hallett V, Lietz S, Garnett T, Ronald A, Plomin R, Rijsdijk F, Happé F, Bolton P. Heritability of autism spectrum disorder in a UK population-based twin sample. JAMA Psychiatry. 2015;72(5):415–423. - PMC - PubMed
    1. Constantino JN. The quantitative nature of autistic social impairment. Pediatr Res. 2011;69:55R–62R. - PMC - PubMed
    1. Constantino JN. Recurrence rates in autism spectrum disorders. JAMA. 2014;312:1154–1155. - PubMed
    1. Constantino JN. Early behavioral indices of inherited liability to autism. Pediatr Res. 2019;85(2):127–133. - PMC - PubMed

Publication types