Potential interactions between coffee consumption, genetic polymorphisms, diabetes, liver and cardiovascular disease, and total and cause-specific mortality

Coffee drinking has been associated inversely with cardiovascular disease, diabetes, liver disease, certain types of cancer, and other diseases. However, there remain concerns about adverse effects, particularly among the large number of so called ?fast metabolizers? who have variants in CYP1A2 and other genes. Our objective is to examine whether associations for coffee drinking with disease vary among people with and without these genetic polymorphisms. Therefore, we propose to 1) identify genetic loci associated with coffee; and 2) examine whether such loci affect associations for coffee and cross-sectional markers of disease, as well as mortality during follow-up. Despite inverse associations with mortality in recent prospective cohort studies, there remains concern that people with certain genotypes may be vulnerable to negative health effects. If verified, prevention strategies can target these carriers who would specifically benefit from coffee restriction. The proposed research will further our understanding of the health impact of coffee and inform dietary guidance regarding coffee consumption. Additionally, this study will provide insight into biological mechanisms underlying previously observed associations of coffee drinking with cardiovascular disease, liver disease, diabetes and mortality by considering the relationships between coffee-drinking genotypes and intermediate markers of chronic disease risk. We will take advantage of already available genetic data to identify particular genetic variants that are associated with coffee drinking, including those related to CYP1A2, confirming and extending previous findings. Then, we will examine associations of coffee drinking with cross-sectional markers of cardiovascular disease, liver disease and diabetes; as well as with total- and cause-specific mortality. Finally, we will examine whether associations between coffee drinking and these disease endpoints vary by the identified genetic variants. The full cohort (N?500,000) will be included in our analysis, including everyone with information on coffee drinking as well as genetic data. Additional analyses including a subset of participants who completed multiple dietary assessments will also be conducted.