Chronic kidney disease (CKD) is a global health problem characterized by a gradual loss of kidney function, increasing the risk of end-stage renal disease, cardiovascular disease, and premature death. Early detection is crucial. Risk factors include hypertension, diabetes, obesity, and genetic factors. Genome-wide association studies (GWAS) are powerful tools for identifying genetic variants associated with complex diseases, allowing for the calculation of genetic risk scores (GRS) to estimate individual risk. Dietary patterns also significantly impact CKD risk; unhealthy patterns increase risk, while healthy patterns reduce it. However, the interplay between genetic and dietary factors in CKD remains unclear. This study aimed to identify genetic risk factors for kidney dysfunction in a Korean population, calculate GRSs, identify dietary patterns, and analyze the interaction between genetic and dietary factors on kidney dysfunction risk. This research aims to inform the development of personalized dietary recommendations for high-risk individuals.

Existing literature highlights the rising prevalence of CKD and its associated comorbidities. Several studies have identified risk factors, including hypertension, diabetes mellitus, and obesity, along with a growing body of evidence supporting the role of genetic factors. GWAS studies have been instrumental in identifying genetic variants linked to CKD risk, leading to the development of GRSs for risk prediction. The influence of dietary patterns on CKD risk is well-established, with studies demonstrating associations between specific dietary patterns (e.g., Western diet) and increased risk. However, research on the interaction between genetic and dietary factors in CKD risk is limited, underscoring the need for this investigation. The ability to personalize dietary interventions based on both genetic predisposition and dietary habits is a crucial area for future research.

This cross-sectional study used baseline data from 8230 Korean adults (aged 40-69) in the Ansan and Ansung Study of the Korean Genome and Epidemiology Study (KoGES). Kidney dysfunction was defined as an estimated glomerular filtration rate (eGFR) <90 mL/minute/1.73 m². Genomic DNA was genotyped using Affymetrix® Genome-Wide Human SNP array 5.0. A GWAS using a generalized linear model was performed on 1,590,162 SNPs, with a P-value threshold of <5 × 10⁻⁸ for significance. Linkage disequilibrium clumping identified 94 significant SNPs, used to calculate individual GRSs. Participants were divided into low-GRS (>0) and high-GRS (≤0) groups. Dietary intake was assessed using a food-frequency questionnaire, and principal component analysis identified three dietary patterns: "prudent pattern," "flour-based and animal food pattern," and "white rice pattern." Multivariable-adjusted logistic regression and joint interaction analyses were used to determine the odds ratios (ORs) and 95% confidence intervals (CIs) of kidney dysfunction across dietary pattern tertiles and GRS groups, adjusting for covariates (sex, age, BMI, etc.).

The GWAS identified 94 SNPs significantly associated with kidney dysfunction, with rs17071575 (ADAMTS9 gene) and rs12242220 (WDFY4 gene) showing the strongest associations. Three distinct dietary patterns were identified. The "flour-based and animal food pattern" showed a significant positive association with kidney dysfunction prevalence in both low and high GRS groups (P for trend <0.0001 in model 1; P for trend = 0.0050 and 0.0065 in model 2 for low and high GRS groups, respectively). The "prudent pattern" showed a borderline inverse association with kidney dysfunction in the low GRS group, but this was not significant after adjustment. The "white rice pattern" showed a significant inverse association in the high GRS group in model 1, but this was not significant after adjustment. Joint effect analysis showed the highest prevalence of kidney dysfunction in individuals with low dietary pattern scores and high GRS. The lowest prevalence was observed in individuals with high "prudent pattern" scores and low GRS.

The significant association between the "flour-based and animal food pattern" and kidney dysfunction prevalence across both GRS groups highlights the importance of dietary modification in CKD prevention, regardless of genetic predisposition. The lack of a strong association between the "prudent pattern" and kidney dysfunction in the high-GRS group after adjustment might be due to the relatively small sample size or the influence of other confounding factors. The identification of ADAMTS9 and WDFY4 as significantly associated genes provides insights into potential biological mechanisms underlying CKD development. The interaction between GRS and dietary patterns underscores the need for personalized nutritional interventions tailored to individual genetic susceptibility and dietary habits. These findings are consistent with other studies showing gene-diet interactions in various diseases, suggesting that personalized approaches are crucial for effective prevention strategies.

This study demonstrates a significant interaction between dietary patterns and genetic susceptibility in the development of kidney dysfunction in a Korean population. The "flour-based and animal food pattern" was strongly associated with higher kidney dysfunction risk, regardless of genetic risk score. Personalized dietary interventions based on GRS and dietary pattern assessment could be a promising approach to prevent and manage CKD. Future research should explore the underlying molecular mechanisms and replicate these findings in diverse populations to improve generalizability and refine prevention strategies.

This study's cross-sectional design limits the ability to establish causality. The reliance on self-reported dietary data introduces potential recall bias. The study population was limited to Korean adults, potentially limiting the generalizability of findings to other ethnic groups. Further research with longitudinal studies and diverse populations is needed to confirm these findings and fully elucidate the complex interplay between genetics and diet in CKD development.