Dietary Patterns, Hepatic Fat Fraction, and the Role of Genotype

Background/Objectives: We aimed to identify eating habits associated with hepatic fat fraction (HFF) and assess effect modification by an established genetic variant for fatty liver disease, PNPLA3 rs738409, among 381 general-risk adolescents. Methods: Dietary intake was assessed using the Block Kids Food Frequency Questionnaire and HFF was measured via magnetic resonance imaging (MRI) at age ~16 years. We first characterized naturally occurring dietary patterns using principal component analysis followed by reduced-rank regression with HFF as the response variable to identify a dietary pattern that is both relevant to the population and associated with HFF. Next, we investigated associations of the dietary pattern with HFF using linear regression models that accounted for maternal gestational diabetes, education, and prenatal smoking and child sex, age, Tanner stage, and BMI. Finally, we tested for a dietary pattern and PNPLA3 rs738409 interaction and stratified by genotype if P-interaction < 0.05. Results: The participants were 16.7 ± 1.2 years (range: 12.6-19.6 years). Half were female (50.4%) and 52.0% identified as non-Hispanic White. The dietary pattern of interest was composed of vegetables, fruit, nuts and seeds, oatmeal, sports bars, crackers and sandwiches, and beef, and was inversely associated with HFF (-0.48 [95% CI: -0.81, -0.16]). Stratified analyses revealed the strongest inverse association observed between the diet pattern score and HFF in the high-risk-variant (GG) group (-2.19 [-4.35, -0.03]), followed by the intermediate-risk (CG) group (-0.43 [-0.77, -0.10]), but not the low-risk (CC) group (-0.32 [-0.77, 0.13]). Conclusions: A diet high in vegetables, fruit, nuts and seeds, oatmeal, sports bars, crackers and sandwiches, and beef-potentially capturing an active, on-the-go lifestyle-is associated with lower HFF during adolescence, especially among individuals at genetic risk.