BackgroundType 2 Diabetes (T2D) and other chronic diseases are caused by a complex combination of many genetic and environmental factors. Few methods are available to comprehensively associate specific physical environmental factors with disease. We conducted a pilot Environmental-Wide Association Study (EWAS), in which epidemiological data are comprehensively and systematically interpreted in a manner analogous to a Genome Wide Association Study (GWAS).Methods and FindingsWe performed multiple cross-sectional analyses associating 266 unique environmental factors with clinical status for T2D defined by fasting blood sugar (FBG) concentration ≥126 mg/dL. We utilized available Centers for Disease Control (CDC) National Health and Nutrition Examination Survey (NHANES) cohorts from years 1999 to 2006. Within cohort sample numbers ranged from 503 to 3,318. Logistic regression models were adjusted for age, sex, body mass index (BMI), ethnicity, and an estimate of socioeconomic status (SES). As in GWAS, multiple comparisons were controlled and significant findings were validated with other cohorts. We discovered significant associations for the pesticide-derivative heptachlor epoxide (adjusted OR in three combined cohorts of 1.7 for a 1 SD change in exposure amount; p<0.001), and the vitamin γ-tocopherol (adjusted OR 1.5; p<0.001). Higher concentrations of polychlorinated biphenyls (PCBs) such as PCB170 (adjusted OR 2.2; p<0.001) were also found. Protective factors associated with T2D included β-carotenes (adjusted OR 0.6; p<0.001).Conclusions and SignificanceDespite difficulty in ascertaining causality, the potential for novel factors of large effect associated with T2D justify the use of EWAS to create hypotheses regarding the broad contribution of the environment to disease. Even in this study based on prior collected epidemiological measures, environmental factors can be found with effect sizes comparable to the best loci yet found by GWAS.

Using data from the National Health and Nutrition Examination Survey, we examine the relationship between nutritional status, poverty, and food insecurity for household members of various ages. Our most striking result is that, while poverty is predictive of poor nutrition among preschool children, food insecurity does not provide any additional predictive power for this age group. Among school age children, neither poverty nor food insecurity is associated with nutritional outcomes, while among adults and the elderly, both food insecurity and poverty are predictive. These results suggest that researchers should be cautious about assuming connections between food insecurity and nutritional outcomes, particularly among children.

Background Since 2003, the President’s Emergency Plan for AIDS Relief (PEPFAR) has been the most ambitious initiative to address the global HIV epidemic. However, PEPFAR’s effect on HIV-related outcomes is unknown. Objective To assess PEPFAR’s impact on HIV-related deaths, the number of people living with HIV, and prevalence in Africa. Design Comparison of trends before and after the initiation of PEPFAR’s activities in the African focus countries with other African countries. Setting Twelve African focus countries and 29 controls with a generalized HIV epidemic from 1997–2007. Observations 451 country-year observations. Intervention A 5-year, $15 billion program for HIV treatment, prevention, and care that started in late 2003. Measurements HIV-related deaths, the number of people living with HIV, and prevalence. Results Between 2004 and 2007, the annual change in the number of HIV-related deaths was lower by 10.5% in the focus countries compared to controls (p=0.001). The difference in trends between the group before 2003 was not significant. The annual growth in the number of people living with HIV was 3.7% slower in the focus countries compared to controls from 1997–2002 (p=0.05), but during PEPFAR’s activities the difference was no longer significant. The difference in the change in HIV prevalence was not significantly different throughout the study period. These estimates were stable after a sensitivity analysis. Limitations The selection of the focus countries was not random, and limits the generalizability of the results. Conclusions We find evidence that, after four years of activity, HIV-related deaths declined in PEPFAR’s focus countries relative to sub-Saharan African controls, but trends in adult prevalence were not different. Assessing epidemiologic effectiveness should be part of PEPFAR’s evaluation programs.

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