PFAS research in the Michigan mother-infant pairs study, supported by ITS, SPH, MM, AGC

PFAS (per- and polyfluoroalkyl substances) are a class of chemicals that have been around since the 1940s and became more broadly used in the post-war 1960s era. PFAS are in our homes, offices, water, and even our food and blood. PFAS break down slowly and are difficult to process, both in the environment and our bodies. 

Scientific studies have shown that exposure to some PFAS in the environment may be linked to harmful health effects in humans and animals. Because there are thousands of PFAS chemicals found in many different consumer, commercial, and industrial products, it is challenging to study and assess the human health and environmental risks. 

Fortunately, some of the most persistent PFAS are being phased out. The EPA has been working on drinking water protections, scientists are working on ways to break down and eliminate PFAS, and PFAS are being addressed at a national level

A team of University of Michigan researchers from the School of Public Health DoGoodS-Pi Environmental Epigenetics Lab and Michigan Medicine are working to understand how behaviors and environments during pregnancy can cause changes to the way genes work in offspring. This emerging field is known as toxicoepigenetics. 

Jackie Goodrich, Ph.D., research associate professor at the U-M School of Public Health, led the team. “PFAS may impact the development of something we all have called the epigenome. The epigenome is a set of modifications on top of our DNA that controls normal development and function. Environmental exposures like PFAS can alter how the epigenome forms, and this impacts development and health. Our study expands on current knowledge about PFAS and the epigenome by focusing on a type of epigenetic mark that is not usually measured.”

Vasantha Padmanabhan, Ph.D., M.S., professor emerita (in service), Department of Pediatrics, Michigan Medicine, built the Michigan Mother-Infant Pairs study over the past decade with an emphasis on identifying harmful exposures during pregnancy that impact women and their newborns. “I am so grateful to those who engaged in this study. PFAS are complex, and mothers’ and infants’ involvement helped us work toward a solution that impacts us all. I want to acknowledge the contributions of the U-M Department of Obstetrics and Gynecology, Michigan Institute for Clinical & Health Research (MICHR), and the Von Voigtlander Women’s Hospital that made this study possible.” 

Rebekah Petroff, Ph.D., a research fellow with Environmental Health Sciences, led the computation portion of the research. She said that using Turbo for storing the raw data and Great Lakes for high-performance computing (HPC) enabled a much faster analysis that was needed for the study with so much data to analyze. 

Turbo and Great Lakes are services provided by Advanced Research Computing, a division of Information and Technology Services (ITS). ARC facilitates powerful approaches to complex research challenges in fields ranging from physics to linguistics, and from engineering to medicine.

Petroff said, “This analysis would have taken over a month straight of computing time on a regular desktop computer. The first job we submitted to Great Lakes ran so fast—I had results the next morning! Great Lakes made this research possible, and I believe that our study results can be broadly impactful to public health and toxicoepigenetics going forward.”

Support for using this complex technology also came from Dan Barker, a UNIX systems admin with the U-M School of Public Health Biostatistics Department. Barker assisted with the code needed to use Great Lakes. “We started with a test run of a few hundred pairs of genomes. Once we were successful with that, we ran the entire nearly 750,000 epigenetic marks across 141 people and seven different PFAS.”

Barker also helped design and submit array jobs which are a series of identical, or near identical, tasks that are run multiple times. This is a common technique used by researchers when leveraging HPC. Array jobs allow for essential analytical comparisons among the test results. Petroff said, “In our study, we used an array job to split up our computations so that they ran much more efficiently!”

The U-M Advanced Genomics Core (AGC) performed the epigenetic assays, a kind of laboratory technique which measures marks on your DNA, for this project. AGC is part of the campus-wide laboratories that develop and provide state-of-the-art scientific resources to enable biomedical research known as Biomedical Research Core Facilities (BRCF). Other BRCF cores also worked on this project, including the Epigenomics Core and the Bioinformatics Core.

Genotyping is similar to reading a few words scattered on a page. This process gives researchers small packets of data to compare. Genotyping looks for information at a specific place in the DNA where we know important data will be. This project used a type of genotyping called microarrays (also known as “arrays”) and help researchers understand how regulation of DNA—including methylation and hydroxymethylation measured in this study—are impacted by exposures like PFAS.  

Brock Palen, ARC director, said, “This research is of human interest and impacts all of us. I’m pleased that ARC assisted their research with staff expertise, equipment, and no-cost allocations from the U-M Research Computing Package.”

Petroff said that follow up studies are needed to better understand if the results are universal or specific to this cohort of infants and parents. If the results hold steady, then a significant discovery has been made that will lead to more comprehensive PFAS mitigation solutions. “Although steps are being taken to mitigate PFAS, exposure is still prevalent, and a deeper understanding of how it impacts humans is needed,” said Dana Dolinoy, Ph.D., chair, NSF International Department Chair of Environmental Health Sciences and epigenetics expert.

Read the full article: Mediation effects of DNA methylation and hydroxymethylation on birth outcomes after prenatal per- and polyfluoroalkyl substances (PFAS) exposure in the Michigan mother–infant pairs cohort.

Funding was provided by grants from the National Institutes of Health, the U.S. Environmental Protection Agency, and the National Institute of Environmental Health Sciences Children’s Health Exposure Analysis Resource program.