An environmental wide association study (EWAS) approach to the metabolic syndrome

Background: Environmental contaminants have previously been linked to components of the Metabolic Syndrome (MetS). However, exposure to environmental contaminants is in part determined by various lifestyle factors.

Objective: Using an "Environmental Wide Association Study" (ELWAS) integrating environmental contaminants and lifestyle factors, we aimed to evaluate a possible additive role of both contaminants and lifestyle factors regarding MetS.

Methods: 1016 subjects aged 70years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. 43 environmental contaminants were measured in the circulation. Dietary records were used to evaluate 21 nutrients and the proportions of 13 fatty acids were determined in serum cholesterol esters to further quantify fat quality intake. Adding 5 other important lifestyle factors yielded together 76 environmental and lifestyle factors. MetS was defined by the NCEP/ATPIII-criteria.

Results: 23% had MetS. Using cross-validation within the sample, fourteen environmental contaminants or lifestyle factors consistently showed a false discovery rate <0.05. When the major variables entered a multiple model, only p, p'-DDE levels (positive), PCB209 (inverse) and exercise habits (inverse) were together with a fatty acid pattern, with high levels of palmitic acid and oleic acid and low levels of linoleic acid, related to MetS (p<0.002 for all variables).

Conclusion: Using a cross-sectional EWAS approach, certain environmental contaminants and lifestyle factors were found to be associated with prevalent metabolic syndrome in an additive fashion in an elderly population.