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Abstract
Environmental factors, and in particular diet, are known to play a key role in the development of Coronary Heart Disease. Many of these factors were unveiled by detailed nutritional epidemiology studies, focusing on the role of a single nutrient or food at a time. Here, we apply an Environment-Wide Association Study approach to Nurses’ Health Study data to explore comprehensively and agnostically the association of 257 nutrients and 117 foods with coronary heart disease risk (acute myocardial infarction and fatal coronary heart disease). After accounting for multiple testing, we identify 16 food items and 37 nutrients that show statistically significant association – while adjusting for potential confounding and control variables such as physical activity, smoking, calorie intake, and medication use – among which 38 associations were validated in Nurses’ Health Study II. Our implementation of Environment-Wide Association Study successfully reproduces prior knowledge of diet-coronary heart disease associations in the epidemiological literature, and helps us detect new associations that were only marginally studied, opening potential avenues for further extensive experimental validation. We also show that Environment-Wide Association Study allows us to identify a bipartite food-nutrient network, highlighting which foods drive the associations of specific nutrients with coronary heart disease risk.
Environmental and dietary factors are known to play a role in the development of coronary heart disease. Here the authors apply a genomic-inspired methodology to Nurses’ Health Study data to explore comprehensively and agnostically the association of 257 nutrients and 117 foods with coronary heart disease risk.
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1 Northeastern University, Center for Complex Network Research, Boston, USA (GRID:grid.261112.7) (ISNI:0000 0001 2173 3359)
2 Harvard T.H. Chan School of Public Health, Department of Nutrition, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
3 Brigham and Women’s Hospital, Channing Division of Network Medicine, Department of Medicine, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294)
4 Harvard T.H. Chan School of Public Health, Department of Nutrition, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Brigham and Women’s Hospital, Channing Division of Network Medicine, Department of Medicine, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294)
5 Northeastern University, Center for Complex Network Research, Boston, USA (GRID:grid.261112.7) (ISNI:0000 0001 2173 3359); Brigham and Women’s Hospital, Channing Division of Network Medicine, Department of Medicine, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294); Central European University, Center for Network Science, Budapest, Hungary (GRID:grid.5146.6) (ISNI:0000 0001 2149 6445)