Environment-Wide Association Studies of Anemia in the National Health and Nutrition Examination Surveys

BackgroundAnemia is a global health problem that can lead to chronic illness in adults and may be fatal in children and the elderly. While some dietary factors and heavy metals are known risk factors for anemia, there are no environment-wide studies of anemia. ObjectivesOur goal was to identify environment-wide risk factors for anemia. MethodsWe evaluated general anemia in children and adults and further classified anemia as a) iron, vitamin B12, or folate deficiency anemia; b) anemia in general chronic diseases; and c) anemia in chronic kidney disease. As well as quantitative measures including level of hemoglobin, serum vitamin B12, red blood cell (RBC) folate, and serum iron. Environment-wide association studies (EWAS) were performed to identify novel environmental risk factors of anemia in discovery and replication subsets of the National Health and Nutrition Examination Surveys (NHANES). ResultsWe identified and replicated 106 potential environmental risk factors for anemia. As expected, serum iron was the top exposure associated with general anemia for adults. Cadmium was associated with adult hemoglobin levels, as were vitamin Bs, micronutrients, smoking, and alcohol consumption. Further, decreased levels of multiple vitamins, including vitamin A, vitamin Es and multiple vitamin Bs, were associated with general anemia in adults. Use of tobacco and alcohol was also found to be associated with red blood cell folate and serum iron levels. In children, serum iron level was associated with folic acid supplements and vitamin A supplements. DiscussionThis is the first EWAS of anemia, providing insights into the environmental etiology of anemia risk in children and adults. These results may lead to the development of public health recommendations to mitigate anemia risk factors.