LATEBREAKER
Genetics
Association of Diet Quality with Nonalcoholic Fatty Liver Disease Varies by Genetic Susceptibility Song-Yi Park* Homa Sadeghi Unhee Lim David Bogumil Lynne Wilkens Veronica W Setiawan Iona Cheng Loïc Le Marchand
A healthy diet is the first-line therapy for nonalcoholic fatty liver disease (NAFLD). However, it remains unknown if the protective effect of a healthy diet on NAFLD varies by genetic susceptibility. In the Multiethnic Cohort (MEC), we previously reported an inverse association between high diet quality as determined by Healthy Eating Index (HEI-2015) score (via self-administrated food frequency questionnaires) and NAFLD risk and developed a polygenic risk score (PRS) with 21 genetic variants for NAFLD in MEC. In this study, we evaluated the cross-sectional HEI-NAFLD association across the PRS levels and carrier status of 21 variants in 542 NAFLD cases (>5% liver fat on magnetic resonance imaging without excessive alcohol intake) and 965 non-cases in the MEC Adiposity Phenotype Study.. We applied logistic regression models adjusted for age, energy intake, total body fat, and population stratification using 5 principal components. We observed significant interaction of HEI with the PRS and carrier status of the PNPLA3 and COBLL1 risk variant (Pinteraction≤0.001). Higher tertiles of HEI, compared with the lowest tertile, were inversely associated with NAFLD in the lower 80% of the PRS [OR for 2nd tertile=0.67 (95% Cl: 0.49-0.91); OR for 3rd tertile=0.51 (0.36-0.72)], while no significant HEI-NAFLD association was detected in the top 20% PRS [ORs and 95% CIs for the 2nd and 3rd tertiles: 1.25 (0.63-2.51) and 0.64 (0.33-1.24) respectively]. Similarly, the inverse HEI-NAFLD associations were more prominent in non-carriers and carriers of one risk allele for PNPLA3 and COBLL1, but not among the carriers of two risk alleles in these loci. In conclusion, our results suggest that the association of a healthy diet with NAFLD differs by genetic susceptibility. If replicated in independent data and prospective studies, this gene-diet interaction can provide important insights to precision intervention strategies to lower the risk of NAFLD.