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Objective  A growing body of evidence suggests that environmental pollutants, such as heavy metals, persistent organic pollutants and plasticizers play an important role in the development of chronic diseases. Most epidemiologic studies have examined environmental pollutants individually, but in real life, we are exposed to multi-pollutants and pollution mixtures, not single pollutants. Although multi-pollutant approaches have been recognized recently, challenges exist such as how to estimate the risk of adverse health responses from multi-pollutants. We propose an “Environmental Risk Score (ERS)” as a new simple tool to examine the risk of exposure to multi-pollutants in epidemiologic research.    Methods and Results  We examined 134 environmental pollutants in relation to serum lipids (total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) and triglycerides) using data from the National Health and Nutrition Examination Survey between 1999 and 2006. Using a two-stage approach, stage-1 for discovery (n = 10818) and stage-2 for validation (n = 4615), we identified 13 associated pollutants for total cholesterol, 9 for HDL, 5 for LDL and 27 for triglycerides with adjustment for sociodemographic factors, body mass index and serum nutrient levels. Using the regression coefficients (weights) from joint analyses of the combined data and exposure concentrations, ERS were computed as a weighted sum of the pollutant levels. We computed ERS for multiple lipid outcomes examined individually (single-phenotype approach) or together (multi-phenotype approach). Although the contributions of ERS to overall risk predictions for lipid outcomes were modest, we found relatively stronger associations between ERS and lipid outcomes than with individual pollutants. The magnitudes of the observed associations for ERS were comparable to or stronger than those for socio-demographic factors or BMI.    Conclusions  This study suggests ERS is a promising tool for characterizing disease risk from multi-pollutant exposures. This new approach supports the need for moving from a single-pollutant to a multi-pollutant framework.

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Environmental Risk Score as a New Tool to Examine Multi-Pollutants in Epidemiologic Research: An Example from the NHANES Study Using Serum Lipid Levels