#1441 Diet-by-polygenic score interaction effects on kidney function

Abstract Background and Aims Chronic kidney disease (CKD) affects 10% of the worldwide population. While diet plays a key role in CKD prevention and management, interaction between diet and CKD genetic predisposition is largely unexplored. We investigated the interplay between a polygenic score (PGS) and dietary patterns in determining the CKD-defining trait, the estimated glomerular filtration rate (eGFR), in the Cooperative Health Research In South Tyrol (CHRIS) study. Method We derived eGFR for 5,717 individuals without CKD and related morbidities (median age: 40 years; 53% females; median eGFR: 101.7 ml/min/1.73 m2). Using data from the GA2LEN food frequency questionnaire, we estimated the CKD-relevant nutrients protein, potassium, and phosphorus, and the overall diet quality as the Dietary Approach to Stop Hypertension (DASH) index. We derived the eGFR PGS using 131 high-quality imputed variants, with effect sizes derived from a large genome-wide association study meta-analysis (n = 1,046,070), and where variants were selected for kidney function relevance and identified using an additive genetic model. We fitted multiply adjusted generalized additive models incorporating tensor product smooths and diet-PGS interaction terms to model non-linear associations with eGFR. Results The PGS explained 1.5% of the eGFR variance. Among dietary exposures, the DASH score explained the largest proportion (2.2%), followed by potassium (1.9%), proteins (1.8%), and phosphorus (0.2%). In all models, the PGS was linearly associated with eGFR (P < 0.0001), regardless of dietary exposures. All nutrients showed statistically significant linear associations with eGFR, while the association with the DASH score was not significant. Proteins and phosphorus showed significant non-linear interactions with the PGS (protein:PGS P = 0.0298; phosphorus:PGS P = 0.0283), indicating that higher intake of these nutrients was associated with lower eGFR levels in individuals with a high PGS but not in those with a low PGS. Conclusion The PGS explained a modest proportion of eGFR variance and interacted significantly with dietary proteins and phosphorus. These findings suggest genetic predisposition to potentially modify the association between protein and phosphorus intake, and kidney function.