Mothers of toddler-age twins from an unselected population judged items reflecting behaviors used to screen for autism. These items were summed to yield scores comparable to M-CHAT scores. The sex ratio for above-threshold screener scores was lower than the typical 4:1 male: female ratio reported for autism diagnoses, and such a ratio was reached only in the range of very extreme scores. Genetic differences played a moderate role and appeared to be stronger for males than females, although this difference might have been due to male scores being more extreme, more variable, and more reliable.
These analyses extend the investigation of heritability to autism indicators during toddlerhood, when behavioral manifestations of autism become apparent and initial diagnoses are made. The genetic influence on categorical scores was moderate for both screener thresholds (44–68% of phenotypic variance) but similar to some estimates in general population studies of school-age children and adolescents using other instruments, and lower than estimates from other studies.2,4–6
Differences in age or assessment instrument may contribute to differences in estimated heritability across studies. For example, the CAST, SRS, and SCDC are parent- and teacher-reported questionnaires for children and adolescents that assess things such as how well the child can maintain a two-way conversation or whether the child has friends rather than only acquaintances. Most of the M-CHAT items assess pointing, looking, and imitation. The developmental links between the early behaviors, assessed by the M-CHAT, and later social interaction are insufficiently understood, and we have little sense of how the influence of relevant genetic and environmental factors might change over time.41–44
To understand fully the implications of each twin study of diagnosed autism or autistic traits, sample characteristics must be scrutinized. Our identification of 2.8% and 1.3% of our toddler sample as above threshold (≥ the equivalent of 2 and 2.5 of the 6 M-CHAT analogous items, respectively) overestimates the number of children expected to qualify eventually for an autism spectrum diagnosis, based on prevalence estimates for the preschool population.45
This over-inclusiveness is acceptable in first-stage screeners such as the M-CHAT, which are intended to identify children for continued evaluation. However, the threshold proposed by the M-CHAT authors might need to be modified, especially if lowering the false positive rate is a priority.7,32
The currently accepted prevalence estimate of 0.006%, if applied to this sample (which is admittedly a questionable application), suggests that 55 of the 69 children scoring above the 2-item threshold but only 19 of the 33 children scoring above the 2.5-item threshold would be false positives.45
Our observed 1.5:1 male: female ratio (for the threshold of 2 items) and 1.8:1 ratio (for the threshold of 2.5 items) differs from the 4:1 ratio commonly observed for diagnosed cases.46
We observed a more skewed (7:1) male: female ratio only when the threshold was raised to the equivalent of 4.5 items. Ronald and colleagues also reported this atypical pattern with the CAST and suggested that different thresholds for males and females might be considered if the goal is for above-threshold scores to reflect the sex ratio of diagnosed autism.33
Conversely, further characterizing young girls who exceed screener thresholds but do not eventually receive a diagnosis would be a novel and potentially fruitful line of inquiry.
We found sex differences in heritability, but the literature on this issue remains mixed. Our sample’s sex ratio increased at extreme screener scores ( and ), and male dimensional scores were more heritable than female scores. However, the male dimensional scores were also more reliable. Higher scale reliability could account for MZ male correlations being higher than MZ female correlations but not for DZ male correlations being lower than DZ female correlations (both of which we observed). The presence of three concordant opposite-sex DZ twin pairs explains the higher correlation observed for opposite-sex DZ twin pairs than same-sex DZ twins (only one concordant pair), although the small numbers involved preclude any strong conclusions about same-sex versus opposite-sex DZ concordance.
Concordance of screener score for all monozygotic and dizygotic twins
The small number of individuals with extreme screener scores makes it difficult to disentangle sex and heritability in our sample, although one explanation for the low male: female ratio we observed might be mothers’ differential expectations for males’ and females’ social and communication skills during toddlerhood. Optimally, male and female scores of equal extremity would be compared to determine whether the evidence implicates difference in heritability due to sex or extreme versus non-extreme scores.
We emphasize that we did not identify children with a current or necessarily future diagnosis of autism, but rather with the presence of early behaviors used in autism screening; indeed, other researchers also suggest that these early behaviors are not confined to individuals who will eventually qualify for an autism spectrum diagnosis.7,30
However, the thresholds used to determine which individuals screen positive are still under consideration. Our results suggest that a slightly higher threshold may identify a more heritable, although still appropriately over-inclusive, number of individuals who screen positive.
Our data collection began prior to the M-CHAT’s publication; however, a major limitation of our study is that we did not use the M-CHAT or the supplemental follow-up interview (although other studies’ protocols have also omitted the interview31
). Although our sample can be defended as large and representative, a key limitation is that the number of above-threshold children is nevertheless modest.
Because our items were chosen to approximate the most discriminative M-CHAT items, and the M-CHAT does not assess restricted/repetitive or stereotyped behaviors or interests, one of the three diagnostic criteria for autism that is more apparent at later ages, our study did not tap this domain either. Thus, another assessment of toddlers that did include all three diagnostic criteria might yield different heritability estimates. However, other researchers have found that repetitive behaviors in one-year-old infants are more accurately linked to developmental delay, rather than autism.47
Like most other investigators, we also relied solely on parental report, which is subject to varying interpretation of items and other biases. Finally, a long-term follow-up of the sample will be needed to establish the screener’s sensitivity and specificity for this population.