presents the distribution of scores for the full sample as well as for individuals identified as extreme scorers within the 95th percentile of each subscale distribution. On average, parents reported the presence of less than two autism-like behaviors per subscale (mean SI=1.62, mean CI=1.92, mean RRBI=1.42). Each of the subscale distributions was positively skewed (SI=1.50, CI=1.38, RRBI=0.92), as expected given the low means relative to the range of scores (SI 0–11, CI 0–12, RRBI 0–7). Mean differences by sex and zygosity were seen in the full sample subscale scores and are noted in detail in . Sex and zygosity together accounted for 5% of variation in SI, less than 1% of variation in CI, and 1% of variation in RRBI.
The mean scores for the greater than 95% extreme-scoring groups were 5.91 (SI), 7.08 (CI), and 4.49 (RRBI), highly similar to the means for the 80 individuals with a DAWBA-identified ASD. These 80 individuals (78.75% male) scored within the top three percent of each of the subscale distributions (mean SI= 6.02, mean CI=7.71, mean RRBI=4.51).
Twin Similarity for Extreme SIs, CIs, and RRBIs
presents the univariate extreme group results for each of the CAST subscales. Overall, the probandwise concordances and extreme group correlations were high for MZ twins in each domain. The MZ concordances (SI 0.53; CI 0.61; RRBI 0.58) were more than twice the DZSS concordances (SI .12; CI 0.21; RRBI 0.24), suggesting additive and possibly nonadditive genetic influences on extreme scores, and no influence of shared environment. As with the probandwise concordances, MZ extreme-group correlations were much larger than the DZ correlations for each symptom type.
Heritability of Extreme SIs, CIs, and RRBIs
The univariate DF model-fitting results are presented in the lower portion of . At age 12, extreme scores within each domain were moderately to highly heritable. The best-fitting SI model suggested moderate heritability (0.58) and moderate unique environmental effects (0.42). The best-fitting DF model for CI indicated high heritability (0.72) and modest unique environmental effects (0.28). The best-fitting RRBI model suggested high heritability for both males (0.74) and females (0.71) and modest unique environmental effects. The shared environmental parameter could be dropped without a significant deterioration in fit in each subscale analysis. The magnitude of heritability did not differ significantly between males and females for any of the subscales. The SI and RRBI models, however, suggested an influence of qualitative sex effects on extreme scores. There was no evidence of qualitative sex effects in the best-fitting CI model.
Genetic and Environmental Overlap between Extreme SIs, CIs, and RRBIs
The bivariate DF results are present in . Each of the six comparisons suggested modest to moderate bivariate heritability of extreme autistic traits. Male estimates of bivariate heritability ranged from 0.28 to 0.49. Female estimates of bivariate heritability ranged from 0.15 to 0.44. Female estimates were lower than male estimates in each of the four comparisons that included social impairment. In the SI→CI and CI→SI comparisons, female estimates of bivariate heritability (0.17, 0.15) were less than half those for males (0.48, 0.49). The female RRBI→SI (0.15) overlap was also approximately half that of the males (0.28). There was a statistically significant interaction between sex and the bivariate heritability parameter in both bivariate SI-CI comparisons (SI→CI, p=0.02; CI→SI, p=0.003). However, after constraining the estimates of bivariate heritability to the MZ transformed cotwin mean, male and female estimates did not differ significantly in magnitude using the confidence interval overlap criterion.
Bivariate Heritability at the Extremes of the General Population
The calculated SI-CI genetic correlation at the extremes was 0.66 for males and 0.24 for females. The male SI-RRBI correlation (0.44) similarly exceeded that for females (0.29). The CI-RRBI correlation was 0.58 for males and 0.57 for females.
Heritability of SIs, CIs, and RRBIs in the General Population
The univariate cross-twin correlations are presented in the top half of . In each domain, the univariate full sample MZ correlations (0.67–0.78) were more than twice the DZ correlations (0.16–0.40), suggesting additive and possibly non-additive genetic effects, and no shared environment, similar to the results of the extremes analysis (). MZ correlations less than unity suggested modest unique environmental effects. The differences between the male MZ and DZ correlations, in each domain, were larger than those between the female MZ and DZ correlations, possibly indicative of quantitative sex effects.
Genetic and Environmental Overlap between SIs, CIs, and RRBIs in the General Population
The cross-twin, cross-trait correlations are presented in the lower half of . The DZ cross-trait correlations (0.02–0.19) were less than those of the MZ (0.16–0.36), suggesting some cross-domain genetic influence on autistic traits. Correlations between the SI and RRBI domains were the lowest for both zygosity groups. The DZSS cross-trait correlations between SI and RRBI were not significantly different from zero (males: r= 0.06, 95% CI −0.001 −0.13; females: r=0.02, 95% CI −0.04 −0.08). For both the SI-CI and RRBI-CI cross-trait correlations, the difference between MZ and DZ males was greater than that between MZ and DZ females, suggesting possible modest quantitative sex effects on bivariate heritability The DZOS correlations were not significantly lower than the combined DZM/DZF cross-trait correlations, suggesting no qualitative sex effects on multivariate etiology.
The best-fitting Cholesky decomposition model is presented in . The ACE Cholesky decomposition model with a sibling contrast term presented in fit better than the saturated model (LRT= 98.5, df= 85, p=0.15). There was a significant sibling contrast in the SI and RRBI domains for females and the RRBI domain for males. Fit statistics for the other Cholesky models that were tested (as described in the Methods section) are available from the first author upon request.
Genetic and environmental overlap in the general population (multivariate ACEs estimates)
Each of the three phenotypic domains was highly heritable in males (72%–76%) and moderately to highly heritable in females (58%–74%). There were no significant shared environmental effects in males. Females displayed significant shared environmental influence in the SI (21%) and CI (3%) domains, but not in the RRBI domain. Modest unique environmental effects were suggested for both males and females in each domain (21–28%).
While genetic effects were substantial within each domain, there was limited genetic overlap between domains. Genetic correlations ranged from 0.23 to 0.40 in males and 0.18 to 0.39 for females. The genetic overlap for both males (rA=0.40) and females (rA=0.39) was strongest between the RRBI and CI domains. The genetic correlation between SI and CI was weakest; the SI-CI genetic correlation in females (0.18, 95% CI 0.18 – 0.20) was significantly lower than that for males (0.32, 95% CI 0.29 – 0.34). Unique environmental correlations were modest (0.00–0.22) for both males and females.