New research by Joachim F. Hallmayer and colleagues released on 4 July 2011 raises questions about how strong a role genetic factors play in causing Autism. A large and careful twin study by Professor Hallmayer’s Stanford University team conducted with the support of the US National Institutes of Health (NIH) found that other factors known as the “shared environment” also influence susceptibility to Autism to a greater degree than previous research had indicated.
In genetics research, outcomes such as Autism can be caused by (a) genes, (b) shared environmental factors, (c) non-shared environmental factors, and (d) various interactions among these first three factors. (Technically, there is also “error,” a factor which is included to allow for some slippage is the relationships among these four.) Genes, of course, can be the same or different; in monozygotic or dizygotic twins they are all the same or 50% the same, respectively. The shared environment for monozygotic twins begins in the womb where they share the same placenta. After they are born, monozygotic twins are more likely to have more shared experiences (e.g., they are more likely to be dressed in matching outfits) than dizygotic twins, so they have a slightly greater shared environment than their dizygotic peer. Non-shared environments are the unique experiences people have; for twins, this factor is pretty minor, and it carries little power or weight. But, back to the chase….
In contrast, for example, to a famous study by A. Bailey and colleagues from 1995 that showed a very high heritability for Autism (92% of monozygotic twins were concordant for Autism but only 10% of dizygotic twins were concordant), the present study found that genetic heritability accounted for only 37% of the variance in Autism and shared environment factors accounted for 55% of Autism disorders. The findings hold whether Autism is diagnosed more strictly or more broadly; when Professor Hallmayer’s team examined Autism Spectrum Disorder cases rather than more narrowly defined cases, the percentages went up to 38% genetic and 58% shared environment contributions.
“High fraternal twin concordance relative to identical twin concordance underscores the importance of both the environment and moderate genetic heritability in predisposing for autism,” Professor Hallmayer said in an NIH press release. He continued, “both types of twin pairs are more often concordant than what would be expected from the frequency of autism in the general population. However, the high concordance among individuals who share only half their genes relative to those who share all of their genes implies a bigger role for shared environmental factors.”
In their article, Professor Hallmayer et al. interpret their findings as evidence of the need for wider studies of the causal factors in Autism in this way:
Our study provides evidence that the rate of concordance in dizygotic twins may have been seriously underestimated in previous studies and the influence of genetic factors on the susceptibility to develop autism, overestimated. Because of the reported high heritability of autism, a major focus of research in autism has been on finding the underlying genetic causes, with less emphasis on potential environmental triggers or causes. The finding of significant influence of the shared environment, experiences that are common to both twin individuals, may be important for future research paradigms. Increasingly, evidence is accumulating that overt symptoms of autism emerge around the end of the first year of life. Because the prenatal environment and early postnatal environment are shared between twin individuals, we hypothesize that at least some of the environmental factors impacting susceptibility to autism exert their effect during this critical period of life. (p. e-7)
According to the authors, their findings encourage researchers to study parental age, birth weight, infections during pregnancy, and other factors that might contribute to Autism. Probably no one of these will be the proverbial “smoking gun,” and the current study does not rule out genetics as a causal factor. At the least, there will be plenty of research to go around.
There is sure to be much debate and discussion about this study. It is the largest study of its kind to date, involving more twins than any similar study of Autism. It is from a reputable research group; Professor Hallmayer and his colleagues have a wealth of experience conducting genetic research and have reported strong methods in detail. And the results are quite different than previous studies’ results.
Whenever new results contrast strongly with long-standing evidence, there is bound to be controversy. It’s a good thing. People will question the study. Sensible people will question the methods, wondering about whether the sample of twins was selected carefully enough (the researchers address some of these questions on page e-7). the statistical techniques (goodness knows, these are more sophisticated than I would be able to defend were it my dissertation meeting!), and so forth. There will probably be some people who will question the researchers motives or parentage; it’s safe to ignore those questions.
It’s wise, in my view, to await replications. This will go on for a while. Here is the abstract followed by citations.
Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism
Context Autism is considered the most heritable of neurodevelopmental disorders, mainly because of the large difference in concordance rates between monozygotic and dizygotic twins.
Objective To provide rigorous quantitative estimates of genetic heritability of autism and the effects of shared environment.
Design, Setting, and Participants Twin pairs with at least 1 twin with an autism spectrum disorder (ASD) born between 1987 and 2004 were identified through the California Department of Developmental Services.
Main Outcome Measures Structured diagnostic assessments (Autism Diagnostic Interview–Revised and Autism Diagnostic Observation Schedule) were completed on 192 twin pairs. Concordance rates were calculated and parametric models were fitted for 2 definitions, 1 narrow (strict autism) and 1 broad (ASD).
Results For strict autism, probandwise concordance for male twins was 0.58 for 40 monozygotic pairs (95% confidence interval [CI], 0.42-0.74) and 0.21 for 31 dizygotic pairs (95% CI, 0.09-0.43); for female twins, the concordance was 0.60 for 7 monozygotic pairs (95% CI, 0.28-0.90) and 0.27 for 10 dizygotic pairs (95% CI, 0.09-0.69). For ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs (95% CI, 0.65-0.86) and 0.31 for 45 dizygotic pairs (95% CI, 0.16-0.46); for female twins, the concordance was 0.50 for 9 monozygotic pairs (95% CI, 0.16-0.84) and 0.36 for 13 dizygotic pairs (95% CI, 0.11-0.60). A large proportion of the variance in liability can be explained by shared environmental factors (55%; 95% CI, 9%-81% for autism and 58%; 95% CI, 30%-80% for ASD) in addition to moderate genetic heritability (37%; 95% CI, 8%-84% for autism and 38%; 95% CI, 14%-67% for ASD).
Conclusion Susceptibility to ASD has moderate genetic heritability and a substantial shared twin environmental component.
Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P,, Simonoff, E., Yuzda, E, & Rutter, M. (1995). Autism as a strongly genetic disorder: Evidence from a British twin study. Psychological Medicine, 25, 63-77.
Hallmayer J., Cleveland S., Torres A., Phillips J., Cohen B., Torigoe T., Miller J., Fedele A., Collins J., Smith K., Lotspeich L., Croen LA., Ozonoff S., Lajonchere C., Grether J. K., & Risch N.(2011). Genetic heritability and shared environmental factors among twin pairs with autism. Archives of General Psychiatry. doi:10.1001/archgenpsychiatry.2011.76