Per-and polyfluoroalkyl substances and disrupted sleep: mediating roles of proteins
Year: 2024
Type: article
Study design: Observational Study
Abstract: • We incorporated epidemiological study with computational toxicology analysis. • PFDA, PFOA, and PFHxS were associated with shorter sleep duration. • PFOS was associated with higher sleep disturbance and sleep-related impairment. • Computational toxicology identified genes associated with both sleep-wake disorder and PFAS. • Mediation analysis confirmed involvement of metabolic and immune-related proteins. Per-and polyfluoroalkyl substances (PFAS) contamination may disrupt sleep through disrupted metabolic and immune functions. The study aims to investigate the association and potential mechanism between PFAS and sleep. We included 136 young adults recruited between 2014-2018 and 76 were re-assessed between 2020-2022. Additional 8 participants only had complete data between 2020-2022. Plasma PFAS (PFOS, PFOA, PFHxS, PFHpS, PFPeS, PFNA, PFDA) were measured at both visits using liquid-chromatography high-resolution mass spectrometry. Plasma proteins were measured by Olink® Explore 384 Cardiometabolic and Inflammation Panel I . Sleep duration was self-reported at both visits along with follow-up sleep disturbance and sleep-related impairment using validated instruments. We utilized multiple linear regression to explore the association between individual PFAS (in tertile) and these sleep outcomes. PFAS associated with sleep outcomes were subjected to computational toxicology analysis using the Comparative Toxicogenomics Database and Toxicology in the 21st Century database to identify potential genetic links between them. Mediation analysis using proteomic data was then performed to confirm the findings from computational toxicology analysis. At baseline, one tertile increase in PFDA was associated with 0.39 (95 % CI: 0.05, 0.73) hours of shorter nightly sleep duration, and, at follow-up, PFHxS and PFOA were associated with 0.39 (95 % CI: 0.05, 0.72) and 0.32 (95 % CI: 0.01, 0.63) hours shorter sleep duration, respectively. One tertile increase in PFOS exposure was associated with a 2.99-point increase in sleep disturbance scores (95 % CI: 0.67, 5.31) and a 3.35-point increase in sleep-related impairment scores (95 % CI: 0.51, 6.20). Computational toxicology and mediation analyses identified potential mediating roles for several proteins in the PFAS-sleep associations, including 11-beta-dehydrogenase isozyme 1 (HSD11B1), cathepsin B (CTSB) and several immune system-related proteins. Future large scale epidemiological and mechanistic studies should confirm our findings and test effect measure modification of the associations by age.
Source: Environmental Advances
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $1,750
Funders: University of Southern California, National Institutes of Health, National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute on Minority Health and Health Disparities
Awards: G1158240635, G123299153, G1292929380, G1410786972, G1480891745, G1583036818, G1711859607, G178614128, Environmental Genomics, Environmental Chemical Exposures and Longitudinal Changes of Glucose Metabolism, Insulin Sensitivity and B Cell Function in Youth, G346198372, G422373627, Developmental origins of child liver injury: Effects of prenatal environmental exposures, G4333704872, G444661368, Effects of DDE exposure on adipose tissue function, weight loss and metabolic improvement after bariatric surgery: A new paradigm for study of lipophilic chemicals, G4849313872, Pediatric Autoimmune Consortium for Exposome Research (PACER), G5163582874, G5229491074, G5672741879, G5682798090, G57626283, G6219585282, G6356692452, G6439865796, G6691903051, G6735180440, G7137192840, G8077727690, G89476839, G8988548338, PFAS Exposure and Diabetic Kidney Disease in Youth with Type 2 Diabetes: A Multi-Omic Approach for Prevention and Treatment, Southern California Center for Children’s Environmental Health Translational Research, Environmental Exposures, Host Factors and Human Disease, Mount Sinai Center for Health and Environment Across the LifeSpan (HEALS), Perfluoroalkyl Substances and the Gut Microbiome and Fecal Metabolome: Implications for Obesity Risk in Hispanic Children, G984942071
OpenAlex ID: W4402564303