Samantha L Kingsley1, Douglas I Walker2, Antonia M Calafat3, Aimin Chen4, George D Papandonatos5, Yingying Xu6, Dean P Jones7, Bruce P Lanphear8,9, Kurt D Pennell10, Joseph M Braun11. 1. Department of Epidemiology, School of Public Health, Brown University, Box G-S121-2, Providence, RI, 02912, USA. 2. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 3. Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA. 4. Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA. 5. Department of Biostatistics, School of Public Health, Brown University, Providence, RI, USA. 6. Division of General and Community Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. 7. Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA. 8. Child and Family Research Institute, BC Children's and Women's Hospital, Vancouver, BC, Canada. 9. Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada. 10. School of Engineering, Brown University, Providence, RI, USA. 11. Department of Epidemiology, School of Public Health, Brown University, Box G-S121-2, Providence, RI, 02912, USA. Joseph_Braun_1@brown.edu.
Abstract
INTRODUCTION: Exposure to perfluoroalkyl substances (PFAS), synthetic and persistent chemicals used in commercial and industrial processes, are associated with cardiometabolic dysfunction and related risk factors including reduced birth weight, excess adiposity, and dyslipidemia. Identifying the metabolic changes induced by PFAS exposure could enhance our understanding of biological pathways underlying PFAS toxicity. OBJECTIVE: To identify metabolic alterations associated with serum concentrations of four PFAS in children using a metabolome-wide association study. METHODS: We performed untargeted metabolomic profiling by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified serum concentrations of perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorononanoic acid, and perfluorohexanesulfonic acid (PFHxS) for 114 8-year old children from Cincinnati, OH. We evaluated associations between each serum PFAS concentration and 16,097 metabolic features using linear regression adjusted for child age, sex, and race with a false discovery rate < 20%. We annotated PFAS-associated metabolites and conducted pathway enrichment analyses. RESULTS: Serum PFAS concentrations were associated with metabolic features annotated primarily as lipids and dietary factors. Biological pathways associated with all four PFAS included arginine, proline, aspartate, asparagine, and butanoate metabolism. CONCLUSIONS: In this cross-sectional study, childhood serum PFAS concentrations were correlated with metabolic pathways related to energy production and catabolism. Future studies should determine whether these pathways mediate associations between PFAS exposure and childhood cardiometabolic health.
INTRODUCTION: Exposure to perfluoroalkyl substances (PFAS), synthetic and persistent chemicals used in commercial and industrial processes, are associated with cardiometabolic dysfunction and related risk factors including reduced birth weight, excess adiposity, and dyslipidemia. Identifying the metabolic changes induced by PFAS exposure could enhance our understanding of biological pathways underlying PFAStoxicity. OBJECTIVE: To identify metabolic alterations associated with serum concentrations of four PFAS in children using a metabolome-wide association study. METHODS: We performed untargeted metabolomic profiling by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified serum concentrations of perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorononanoic acid, and perfluorohexanesulfonic acid (PFHxS) for 114 8-year old children from Cincinnati, OH. We evaluated associations between each serum PFAS concentration and 16,097 metabolic features using linear regression adjusted for child age, sex, and race with a false discovery rate < 20%. We annotated PFAS-associated metabolites and conducted pathway enrichment analyses. RESULTS: Serum PFAS concentrations were associated with metabolic features annotated primarily as lipids and dietary factors. Biological pathways associated with all four PFAS included arginine, proline, aspartate, asparagine, and butanoate metabolism. CONCLUSIONS: In this cross-sectional study, childhood serum PFAS concentrations were correlated with metabolic pathways related to energy production and catabolism. Future studies should determine whether these pathways mediate associations between PFAS exposure and childhood cardiometabolic health.
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