Autism Study Advances Understanding of Gene-Environment Interactions

New study uses brain tissue to deepen understanding of the roles that genetics and environment play in autism spectrum disorder

A new study using human brain tissue from the Autism Tissue Program (ATP), an Autism Speaks translational research program, identifies new genes of interest in understanding the genetic and environmental interaction in ASD. Appearing in the recent issue of Molecular Psychiatry, the study conducted by six researchers from Johns Hopkins, analyzed tissue from multiple areas of the brain known to be affected by autism.

Using sensitive technologies, the study is the first to identify specific areas of genetic information in the genome in brain tissue that are abnormally methylated in individuals with ASD. Methylation is one way in which gene expression is changed through environmental exposures. “These findings show that chemical changes to the DNA are different in brains from autistic individuals.  Since methylation can be modified by environment, and also helps regulate how genes are used in the body, these particular areas of the genome may give us leads about how environment manifests biological risk for autism,” says M. Daniele Fallin, Ph.D, an epidemiologist and study coauthor.

The study examined postmortem brain tissue from 19 autism cases and 21 unrelated controls with the intent of further understanding the way epigenetics—key regulators of gene expression—determines whether or not a youngster will develop ASD.

Researchers identified four areas of genes that have different epigenetic patterns in cases and controls and may thus be responsive to the environment—that is, they may be able to “turn on” or “turn off” gene expression following different environmental exposures. They also independently replicated their findings to show the effect was stable.

“While the samples in this study were obtained well after birth, recent studies have shown that changes to genetic DNA could reflect prenatal exposure that persists into childhood or adulthood,” says Alycia Halladay, senior director of clinical and environmental sciences at Autism Speaks.

This study identified new gene regions, which were independently tested to consistently demonstrate the difference between regulation of gene expression in people with autism when compared to control individuals.

Further, the autism-associated genetic regions subject to change may be influenced by both changes to the genes or environmental exposures. This broadened landscape holds promise for future research, the study authors say. “We are still trying to understand how both genetic predisposition and developmental environment interplay to cause autism,” says Fallin. “Identification of genomic regions that show differences in epigenetic gene regulation, which may be influenced by environment, may help bring together environmental and genetic hypotheses in autism research.”

While this study did not examine specific environmental factors, previous scientific findings have suggested influences such as stress, chemicals, and certain toxicants play a role in the way genes are expressed.   “Epigenetics is an understudied area in the field of gene/environment interactions, and these are important findings in better understanding how the environment contributes to the risk of autism,” says Halladay.

This work was supported by funding from National Institutes of Health Centers of Excellence in Genomic Science, 5P50HG003233 to APF and Department of Defense (CDMRP) AR080125 to APF and WEK. Tissue was supplied by the Autism Tissue Program and the NICHD Brain and Tissue Bank.

Fallin is the recipient of the Autism Speaks Geier Grant in Environmental Research. Through this grant, she is studying specific environmental factors.