Guest post by genetic epidemiologist Christine Ladd-Acosta. In her research, Dr. Ladd-Acosta collaborates with Dani Fallin, director of the Wendy Klag Center for Autism and Developmental Disabilities at the Johns Hopkins Bloomberg School of Public Health. The group’s research is supported by several grants from Autism Speaks.
I’ve always had a passion for the health and wellbeing of children and their families. So it was a natural fit when I began working with Dr. Fallin here at Johns Hopkins.
Primarily, our work focuses on examining genetic and environmental risk factors for autism. In the process, we are deepening our understanding of autism’s underlying biology. (Editor’s note: Also see “What do scientists mean by environmental risk factors for autism?”)
Much of this research is supported by the National Institutes of Health. However, there are gaps in this government funding, as is often the case with research that pursues new ideas. Autism Speaks has provided critical additional funding that is enabling us to move the larger field of autism research in exciting new directions. I would like to highlight a few of these projects.
Geier Autism Research Grant in Environmental Sciences
Thanks to an Autism Speaks’ Philip and Faith Geier Autism Research Grant in Environmental Sciences, we are studying DNA methylation in a large group of children with autism as well as a comparison group of children without the disorder.
As many readers of this blog column know, DNA methylation is one of the epigenetic mechanisms that regulates when and where specific genes turn on and off in our brains and bodies. I think of methylation as a light switch: It sits on top of the electrical wires – the gene’s DNA sequence. Adjusting the methylation switch changes whether the light – that is, the gene – is on or off. (Also see “What is epigenetics, and what does it have to do with autism?”)
We know that a tightly coordinated sequence of gene activity is crucial to early brain development. So we are particularly concerned about environmental influences that may turn genes on or off at the wrong times in the developing brain. In particular, we’re following up on research that implicates such environmental influences as maternal infection during pregnancy and chemical exposures during pregnancy and infancy.
The children enrolled in this investigation are part of the national Study to Explore Early Development (SEED). Funded by the Centers for Disease Control and Prevention, SEED recruits thousands of families across the United States.
Our Autism Speaks Geier grant enabled us to add DNA methylation measurements to this study. As a result, we now have a large unified body of information on a subset of the SEED children. This information includes genetic, epigenetic and environmental exposure data as well as medical information on both mothers and children.
This research is enabling us to tease apart which environmental exposures and which gene sequences control DNA methylation. Importantly, we need to understand the interrelated roles these factors play in autism.
For example, does having a certain gene variation increase the effect of certain environmental exposures?
Why focus on prenatal development?
We focus strongly but not exclusively on prenatal events because we know this is a crucial time in brain development. We have also discovered DNA methylation patterns in 3 to 5 year old children that appear to be signatures of environmental exposures that occurred during their prenatal development. This discovery may be a big advance not only for autism research but also for the larger field of environmental health research.
Our Early Autism Longitudinal Investigation (EARLI) enrolls pregnant women who already have a child with autism. Because autism tends to run in families (the genetic part), we know these babies will be at higher than normal risk for developing autism. Of course, we’re not alone in studying “baby sibs.” We are following the same model of many researchers who are part of the Autism Speaks Baby Siblings Research Consortium.
Here at Johns Hopkins, we’re able to focus on very early genetic and environmental risk factors by beginning our tracking during pregnancy. We do so by taking blood and urine from the mother during pregnancy and samples of household dust. We again take samples – from both mother and baby – at birth. And we continue with blood, urine, and even breast milk samples between ages 6 months and 3 years.
In analyzing these samples, we’re looking for relationships between environmental exposures in pregnancy and both genetic predisposition and DNA methylation in both mother and child. Though complex, such analyses are so important for answering questions about gene-environment interactions in the development of autism.
Studies that enroll mothers and children during pregnancy and early childhood are particularly valuable in autism research. They allow us to collect information on environmental exposures as they occur. This eliminates the uncertainties that result from having to rely on recall of past events and other major gaps in the information we need.
At this year’s International Meeting for Autism Research (IMFAR), we presented important early findings from this research. We found differences in DNA methylation at birth between children who went on to develop typically and those who showed development difficulties. We used a standardized measure – the Autism Observation Scale in Infancy (AOSI) for these measurements.
Our EARLI-IBIS collaboration
The time-intensive and costly nature of our research reduces the number of families we can follow. For this reason, it’s so important for us to join forces with other researchers doing similar studies. Together we can increase our ability to detect associations.
This collaboration enables our two groups to align how we collect information, perform genetic analysis and carry out other aspects of our work. The result: A larger sample size for both groups, which in turn increases the depth and reliability of our results.
By working together with the IBIS team, we’re able to link many layers of information – from genetics and epigenetics to the physical unfolding of nerve-cell connections and brain structures. We are excited by the potential to further understand autism’s complex biology in ways that may lead to new treatments and supports for individuals living with autism.
We would like to thank Autism Speaks community of supporters – along with all the families participating in SEED, EARLI, and IBIS – for making this work possible.
Explore all the research and family-service projects that Autism Speaks is funding using this website’s grant search.
These projects are made possible by the passion and generosity of our families, donors and volunteers.
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