Long-standing interest has been put on the health effects of environmental and metabolic risk factors through biological mechanisms involved in metabolic pathways including ROS, hormones, inflammation, energy metabolism, gene expression regulation, immunity, and cell cycle/proliferation. Environmental and metabolic risk factors have key roles in diseases including diabetes, cancer and cardiovascular diseases, which may account for over 80% of all deaths worldwide. In addition to investigate individual factors, investigations of combined risk factors on disease and mortality risk have gained substantial attention given their synergistic or antagonistic effects. Therefore, integrated analyses of dietary behaviors, lifestyle, social and natural environment, physical examination and laboratory biomarkers, which represent more diverse and multi-dimensional exposures, are needed to investigate potential etiologies of chronic diseases and facilitate translational health-care policies. Moreover, interactions between genetic variation and above risk factors have been shown for risk of chronic diseases including cancer and mortality that may shed light on the biological mechanisms and deserve greater attention. Beyond the above-mentioned beneficial chronic disease health associations, it is of timely importance to determine whether these factors are associated with the risk of COVID-19 and death, and have any potential preventative potential against infection and progression.
The overall aim of this proposal is to comprehensively examine associations of environmental and metabolic risk factors and the interactions with genetic susceptibility loci with risk of COVID-19, chronic diseases and mortality. Specifically, we aim to: 1) Assess associations of dietary behaviors, lifestyle, natural and social environment, physical examination and laboratory biomarkers with risk of COVID-19, cancer, diabetes, and overall and cause-specific mortality; 2) Evaluate whether genetic variants can modify the associations of dietary behaviors, lifestyle, natural and social environment, physical examination and laboratory biomarkers with risk of COVID-19, chronic diseases and mortality; 3) Explore whether age, gender, racial/ethnic group, genetic background, and other selected factors can modify the associations of dietary behaviors, lifestyle, natural and social environment, physical examination and laboratory biomarkers with risk of COVID-19, chronic diseases and mortality. Project duration will be 36 months and it might be extended given advances in statistical methodology and additional validation of findings. Our findings may provide evidence that environmental and metabolic factors and possible modification may impact long-term health outcomes as well as risk and prognosis for COVID-19 infection. The project should also facilitate development of standards of medical care, promote translational findings into health-care policies and contribute to ongoing informed public health practices.