Abstract P095: Diet Quality and Genetic Association With Body Mass Index

Background: Whether dietary quality modifies genetic association with body mass index (BMI) is unknown. Methods: We examined the interactions prospectively of a genetic risk score (GRS) based on 97 BMI-associated variants with three diet quality scores (alternative healthy eating index 2010 (AHEI-2010), Alternative Mediterranean Diet score (AMED) and Dietary Approach to Stop Hypertension (DASH) diet score) on BMI in 30,904 participants from three large US cohorts. According to the enrichment of genes near the BMI-associated loci in the central nervous system (CNS), we further created two subsets of GRSs: CNS GRS based on 54 variants and non-CNS GRS based on 43 variants. Findings: We found significant interactions between total GRS and all three diet scores on BMI assessed after 2 to 3 years, with an attenuated genetic effect observed in individuals with healthier diets (AHEI: P for interaction = 0.003; AMED: P = 0.001; DASH: P = 0.004). For example, the difference in BMI per 10 unit increment of the GRS was smaller among participants in the highest tertile of AHEI score compared to those in the lowest tertile (0.84 [95% CI: 0.72, 0.96] vs. 1.14 [0.99, 1.29] kg/m 2 ). Results were consistent across the three cohorts with no significant heterogeneity. The interactions with diet scores on BMI appeared more significant for CNS GRS (AHEI: P = 0.009; AMED and DASH: P < 0.001) than for non-CNS GRS (AHEI: P = 0.10; AMED: P = 0.50; DASH: P = 0.68). Among individual components of diet scores, higher consumption of red/processed meat, sugar-sweetened beverages, and trans fat accentuated genetic associations with BMI (P <0.01), while higher consumption of fruit and moderate alcohol attenuated genetic associations with BMI (P < 0.01). Interpretation: A higher diet quality may mitigate genetic predisposition to obesity. These findings provide insights into complex interplays between diet and genetic influences and underscore the importance of adopting a healthful diet for the prevention of obesity, particularly those individuals with a strong genetic predisposition to obesity.