Abstract
Background/Objectives:
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 creatinine-based estimated glomerular filtration rate (eGFR), in the Cooperative Health Research In South Tyrol (CHRIS) study.
Methods:
We derived eGFR on 5,975 individuals without CKD and related morbidities (median age: 40 years; 53% females; median eGFR: 101.6 ml/min/1.73m2), who completed the GA2LEN food frequency questionnaire. We estimated four CKD-relevant nutrients (protein, potassium, sodium, phosphorus) and the Dietary Approach to Stop Hypertension (DASH) index, reflecting overall diet quality. The PGS was derived from a large genome-wide association study meta-analysis (n=1,046,070), applying the PRS-CS algorithm, controlling for population structure via continuous shrinkage correction (959,833 common variants with high imputation quality). We fitted multiply-adjusted generalized additive models incorporating tensor product smooths and diet-PGS interaction terms to model non-linear associations with eGFR.
Results:
PGS and DASH index explained 5.6% and 2.3% of eGFR variance, respectively. eGFR resulted non-linearly associated with PGS (P<0.0001) and DASH index (P=0.042) and linearly associated with all nutrients but sodium. We observed significant interaction of the PGS with protein intake (P=0.028) and protein-corrected phosphorus levels (P=0.007): high protein intake was associated with lower eGFR in individuals with high PGS but not in those with low PGS.
Conclusion:
Genetic predisposition may modify the association between protein intake and kidney function.