(OR27-02-24) Changes in Carbohydrate Intake, Genetic Risk, and Long-Term Weight Change

Objectives: To examine whether genetic risk of obesity modifies the association between changes in carbohydrate intake and weight change, and to identify specific genetic loci that affect how body weight responds to changes in carbohydrate intake.

Methods: Our analysis included 27,887 participants from 3 longitudinal cohorts of adults. Carbohydrate exposures, including total carbohydrates, glycemic index, glycemic load, and different types of carbohydrates, were derived from validated food frequency questionnaires updated every 4 years. Participants self-reported body weight biannually over follow-up. We estimated the interactions of a genetic risk score (GRS) based on 96 body mass index (BMI)-associated variants on the association of 4-year changes in carbohydrate intake and concurrent weight change. We additionally conducted a genome-wide association study (GWAS) analysis to identify genetic variants associated with the response of weight change to changes in carbohydrate intake; response was estimated by a linear mixed-effect model.

Results: As intended, the BMI GRS was associated with weight gain over follow-up (0.16 kg [95% CI: 0.08, 0.24] over 4 years comparing extreme quintiles, P trend < 0.001). We observed statistical interactions between GRS and changes in glycemic index, starch intake, and total glucose equivalents (from glucose monosaccharides, disaccharides, and starch) in relation to weight change (all P for interactions < 0.01). Changes in these carbohydrate exposures were related to greater weight gain among participants with higher GRS compared to lower GRS. For example, a 10-unit increase in the glycemic index of overall diet was associated with a weight change of 1.4 kg (95% CI: 1.2, 1.7) among participants in the highest quintile, compared to 0.8 kg (95% CI: 0.6, 1.0) among those in the lowest. GWAS analysis identified genetic loci near the NADPH oxidase 3 gene being significantly associated with the response of weight change to changes in total glucose equivalents and starch intake (P < 5x10^-8).

Conclusions: Our findings suggest that individuals at a greater genetic risk for obesity are more prone to the adverse effects of having a diet with a high glycemic index and a high intake of starch and total glucose equivalents on weight gain.

Funding Sources: National Institutes of Health, Friends of FACES/Kids Connect