Chris Gennings, PhD
Research Professor; Director of the Division of Biostatistics
Department of Environmental Medicine and Public Health, Division of Biostatistics
Icahn School of Medicine at Mount Sinai, New York, NY
Abstract: Environmental exposures to a myriad of chemicals are associated with adverse health effects in humans. On the other hand, single chemical in vivo and in vitro studies demonstrate causal links between the chemicals and outcomes, but such studies do not represent human exposure to environmental mixtures. We will present two approaches for including human relevant exposures in steps towards risk assessment of mixtures.
We proposed linking epidemiological association with experimental evidence, where the effect of a human-relevant reference mixture (based on a Swedish pregnancy cohort) on thyroid hormone signaling was assessed and a point of departure (PoD) was derived. Toxicokinetic models were used to compare exposures of women of reproductive age in the US population to the reference mixture using a Similar Mixture Approach (SMACH). Based on our findings, 66% of women of reproductive age in the US (roughly 38 million women) had exposures sufficiently similar to the reference mixture. For this subset, a Similar Mixture Risk Index (SMRIHI) was calculated comparing their exposures to the PoD. Women with SMRIHI > 1, an indication of concern, represent 1.1 million women of reproductive age in the US. These findings indicate that a reference mixture of chemicals identified in a Swedish cohort—and tested in an experimental model for establishment of (PoDs)—is also of health relevance in a US population.
In a second study, our objective was to demonstrate the use of an index as a metric for more causally linking human exposure to health outcomes using observational data. One way of summarizing the effect of the joint action of chemical mixtures is through an empirically weighted index using weighted quantile sum (WQS) regression. In addition, My Nutrition Index (MNI) is a personalized metric of overall dietary nutrition based on guideline values, including for pregnant women. We used both a WQS index of 26 endocrine-disrupting chemicals (EDCs) and MNI using data from a pregnancy cohort to conduct causal inference using g-computation with counterfactuals. In counterfactuals a one standard deviation change in the index (i.e., decrease in the WQS index or increase in MNI) indicated significant improvement in cognitive function. Evaluation of such a strategy may support decision makers for risk management of EDCs and individual choices for improving dietary nutrition.
About the speaker: Dr. Chris Gennings is Director of the Division of Biostatistics and Research Professor in the Department of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai and holds a secondary appointment as Research Professor in the Department of Population Health Science and Policy. Prior to joining Mount Sinai in 2014, Dr. Gennings held positions at the Virginia Commonwealth University, including as Professor in the Department of Biostatistics and Director for the Research Incubator for the Center for Clinical and Translational Research.
An expert in mixtures statistics, Dr. Gennings has been actively engaged in the field for more than 30 years. Her research interests have focused on design and analysis methodologies for studies of chemical mixtures. This has included methods for both toxicology and epidemiology/clinical studies. Recent work includes development of a body burden index with empirically derived weights linked to health outcomes; development of a holistic measure of wellness using biomarkers of effect; development of a nutrition index; development of weighted quantile sum (WQS) regression – a method that is robust to confounding concerns based on complex correlations among exposure to environmental mixtures; and the development of tests for sufficient similarity, a novel approach that complements current cumulative risk assessment methods and does not require the default assumption of additivity.
Thursday, February 15, 2024, 12:00-1:15pm Eastern
Field Auditorium, Room 1112, Grainger Hall (9 Circuit Drive, Durham, NC)
This seminar will also be presented live via Panopto. Click HERE to join the livestream.