308-OR: Genome-Wide Association Study of Food Frequency Questionnaire Single Nutrients and Dietary Patterns Uncover Hundreds of Genetic Associations

Abstract

Unhealthy dietary habits are leading risk factors for type 2 diabetes (T2D) and related traits. However, there has been limited success in the use of traditional dietary measures in genetic, epidemiological, and clinical translation studies thus far, highlighting the potential for exploring complex and genetically based dietary habits. We leveraged quantitative traits and extensive correlation structure from food frequency questionnaires in UK Biobank, one of the largest cohorts of diet and genetics collected to date (N~500K), to derive dietary habits that encompass both single nutrients and principal component (PC) dietary patterns. Dietary patterns summarize correlated food intake into single factors that better represent true dietary habits and thus can translate well into diabetes care and prevention. For example, dietary pattern PC1, similar to “prudent” and “Western” factors as have been previously described, separate individuals that consume more whole meal bread, produce, fish, and water from those that consume more white bread, processed meat, and butter and oil spreads. Overall, we found that 84% of 170 derived dietary habits had a significant genetic component, and genome-wide association studies of 143 significantly heritable dietary habits identified 814 independent genetic loci surpassing genome-wide significance (5.0×10-8). Among these include genetic loci previously associated with T2D, BMI, HDL cholesterol and triglyceride levels, coronary artery disease, physical activity, and macronutrient intake as well as several novel loci. A better understanding of the genetic architecture of diet will undoubtedly be of value to the diabetes community, for which these discoveries lay the foundation for research on biological mechanisms of diet, interaction with known genetic and environmental diabetes risk factors, and advancement on dietary intervention and prevention plans for diabetes. Disclosure J.B. Cole: None. A. Leong: None. J. Hirschhorn: Board Member; Self; Camp4 Therapeutics. J.C. Florez: None. Funding American Diabetes Association (1-19-PDF-028 to J.B.C.); National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK110919-02)