Abstract 26: Polygenic Risk Score for Obesity Modifies Associations of Proinflammatory Diets With Obesity, Long-term Weight Gain, and Cardiovascular Disease Risk: The Utilization of Polygenic Prediction in 3 US Prospective Cohorts

Background: Individuals predisposed to higher genetic risk of obesity may need early dietary interventions to prevent obesity and its comorbidities. Hypothesis: Proinflammatory diets may interact with genetic background to modify risks of obesity, long-term weight gain, and cardiovascular disease (CVD). Methods: We prospectively followed 16 281 and 11 832 women in the Nurses’ Health Study I and II, and 10 172 men in Health Professionals Follow-up Study, with available genetic data, for up to 28 years. Diet and weight were assessed every 4 years. Dietary inflammatory potential was assessed by an empirical dietary inflammatory pattern (EDIP) score pre-defined based on associations of foods with inflammatory markers. Polygenic risk scores (PRS) of body mass index (BMI), waist-hip ratio, and body fat mass, developed based on genome-wide association data of 9 million variants in 389 972 UK Biobank participants using LDpred, were applied to characterize genetic predispositions to obesity, central obesity, and adiposity. Results: All 3 PRS were highly predictive for BMI ( Fig. A ). In pooled multivariable analyses, higher EDIP scores were associated with a higher BMI, with the association 2-3 folds stronger comparing participants in the highest 10% to the lowest 10% of genetic risk of obesity/adiposity ( P interaction ≤0.001; Fig. B ). The positive association between EDIP and CVD incidence was 1.6-fold stronger in participants at a higher genetic risk of central obesity ( P interaction =0.04; Fig. C ). In addition, an increase in EDIP scores was associated with a greater long-term weight gain, while a reduction in EDIP was associated with a greater weight loss, comparing participants in the highest 10% of genetic risk to those at lower risks, among participants aged <65 years but not above ( P interaction <0.005; Fig. D ). Conclusions: Polygenic background modifies associations of proinflammatory diets with obesity, long-term weight change, and CVD risk. PRS may be useful tools to identify individuals in need for early dietary interventions.