An analysis of 100 million U.S. medical records reveals that autism and intellectual disability rates are correlated at the county level with incidence of genital malformations in newborn males, an indicator of possible congenital exposure to harmful environmental factors such as pesticides.
After adjustment for gender, ethnic, socioeconomic and geopolitical factors, autism rates and intellectual disability rates jump substantially for every 1% increase in frequency of malformations in a county, according to the study. Increases in autism and ID rates also are seen in wealthier and more urban counties.
The study, published by scientists from the University of Chicago on March 13 in the open-access journal PLOS Computational Biology, also confirms the dramatic effect of diagnostic standards, according to the researchers. Incidence rates for autism and intellectual disability on a per-person basis decrease by roughly 99% in states with stronger regulations on diagnosis of these disorders.
Autism appears to be strongly correlated with rate of congenital malformations of the genitals in males across the country, study author Andrey Rzhetsky, PhD, professor of genetic medicine and human genetics at the University of Chicago, said in a news release. This gives an indicator of environmental load, and the effect is surprisingly strong.
Study methodology and results
Although autism and intellectual disability have genetic components, environmental causes are thought to play a role. To identify potential environmental links, Rzhetsky and his team analyzed an insurance claims dataset that covered nearly a third of the U.S. population. They used congenital malformations of the reproductive system in males as an indicator of parental exposure to toxins.
Male fetuses particularly are sensitive to toxins such as environmental lead, sex hormone analogs, medications and other synthetic molecules. Parental exposure to these toxins is thought to explain a large portion of congenital reproductive malformations, such as micropenis, hypospadias (urethra on underside of the penis), undescended testicles and others.
The researchers created a statistical baseline frequency of autism and intellectual disability across the country. They then looked at the actual rates of these disorders, county-by-county. Deviations from the baseline are interpreted as resulting from local causes. Factors such as age, ethnicity, socioeconomic groups and geopolitical statuses were analyzed and corrected for.
The team found that every 1% increase in malformations in a county was associated with a 283% increase in autism and 94% increase in intellectual disability in that same county. Almost all areas with higher rates of autism also had higher rates of intellectual disability, which the researchers believe corroborates the presence of environmental factors.
In addition, the researchers found that male children with autism are almost six times more likely to have congenital genital malformations. Female incidence was linked with increased malformation rates, but weakly so. A county-by-county map of autism and intellectual disability incidence above or below the predicted baseline for the entire U.S. is included in the study.
Impact of diagnostic standards
The most striking negative effect was state regulation. State-mandated diagnosis of autism by a clinician for consideration in special education was linked with about a 99% decrease in the rate of incidence for autism and intellectual disability. Certain ethnic backgrounds, such as Pacific Islanders, had significantly lower risk for both diseases.
Although the effect of vaccines was not analyzed as part of the study, Rzhetsky noted that the geographic clustering of autism and intellectual disability rates is evidence that if vaccines have a role, it is a weak one given that vaccinations are given uniformly across the U.S.
Rzhetsky acknowledged potential confounders to the study, such as the fact that ease of access to data could differ between counties or that uneven genetic distribution could have an effect beyond the factors that were controlled for. The team anticipates future studies could leverage data from the Environmental Protection Agency and other sources to identify links between specific environmental causes and increased rates of autism and intellectual disability.
We interpret the results of this study as a strong environmental signal, Rzhetsky said. For future genetic studies we may have to take into account where data were collected, because its possible that you can get two identical kids in two different counties and one would have autism and the other would not.