David Reif, Ph.D., Robert Tanguay, Ph.D.
North Carolina State University, Oregon State University
U01ES027294, P42ES005948, P30ES025128, P42ES016465, T32ES007329
NIEHS grantees developed a new method to identify individual-level genetic variation in response to chemical exposures. The approach, which linked zebrafish studies and bioinformatic approaches, might help identify new genetic factors that explain differences in chemical sensitivity.
To find chemicals with patterns of differential biological responses, the researchers analyzed high-throughput screening data from zebrafish exposed to thousands of individual chemicals. Instead of focusing on particular compounds, the team looked at individually sequenced zebrafish from a diverse population and sought differences in susceptibility.
The screening data pointed to abamectin, a commonly used antiparasitic, as a candidate chemical in which exposure produced different responses in zebrafish. The researchers generated genome-wide sequence data for individual zebrafish that were susceptible or resistant to effects of abamectin exposure. That data led them to a genetic region known as sox7 that was associated with the gene-environment effect. Targeted follow-up experiments confirmed that the susceptible zebrafish expressed a lower level of the sox7 gene than the resistant individuals.
According to the authors, the approach provided a quick way to sort through the exposome of chemicals and to look for relationships between genetics and environmental exposure, rather than being limited to preselected candidate exposures. The ability to identify individual-level genetic variation that affects response to individual chemical environments may bring new precision to personalized toxicity prediction and understanding of how risk may differ across communities.
Citation: Balik-Meisner M, Truong L, Scholl EH, La Du JK, Tanguay RL, Reif DM. 2018. Elucidating gene-by-environment interactions associated with differential susceptibility to chemical exposure. Environ Health Perspect 126(6):067010.