Diet quality and genetic association with body mass index: results from 3 observational studies

Abstract

It is unknown whether dietary quality modifies genetic association with body mass index (BMI). This study examined whether dietary quality modifies genetic association with BMI. We calculated 3 diet quality scores including the Alternative Healthy Eating Index 2010 (AHEI-2010), the Alternative Mediterranean Diet score (AMED), and the Dietary Approach to Stop Hypertension (DASH) diet score. We examined the interactions of a genetic risk score (GRS) based on 97 BMI-associated variants with the 3 diet quality scores on BMI in 30,904 participants from 3 large cohorts. We found significant interactions between total GRS and all 3 diet scores on BMI assessed after 2-3 y, with an attenuated genetic effect observed in individuals with healthier diets (AHEI: P-interaction=0.003; AMED: P=0.001; DASH: P=0.004). For example, the difference in BMI (kg/m2) per 10-unit increment of the GRS was smaller among participants in the highest tertile of AHEI score compared with those in the lowest tertile (0.84; 95% CI: 0.72, 0.96 compared with 1.14; 95% CI: 0.99, 1.29). Results were consistent across the 3 cohorts with no significant heterogeneity. The interactions with diet scores on BMI appeared more significant for central nervous system GRSs (P<0.01 for 3 diet scores) than for non-central nervous system GRSs (P>0.05 for 3 diet scores). A higher diet quality attenuated genetic predisposition to obesity. These findings underscore the importance of maintaining a healthful diet for the prevention of obesity, particularly for those individuals with a strong genetic predisposition to obesity. This trial was registered with the Clinical Trial Registry as NCT03577639.