Assessing genetic causal relationship between milk fat content and chronic kidney disease: a two-sample Mendelian...

Area of Science:

• Nutritional Epidemiology
• Genetic Epidemiology
• Nephrology

Background:

• Chronic kidney disease (CKD) is a significant global health concern.
• Dietary factors, including milk fat content, are suspected contributors to CKD.
• Understanding the genetic basis of this relationship is crucial for targeted interventions.

Purpose of the Study:

• To investigate the potential genetic causal relationship between milk fat content and the risk of developing CKD.
• To utilize genome-wide association study (GWAS) data and Mendelian randomization (MR) for robust causal inference.

Main Methods:

• A two-sample Mendelian randomization (MR) approach was employed using summary statistics from GWAS.
• Inverse variance weighting (IVW) was the primary analysis method, supplemented by MR-Egger, weighted median, and other sensitivity analyses.
• Rigorous quality control and sensitivity analyses (e.g., Cochran's Q, MR-Egger intercept, leave-one-out) were performed to assess heterogeneity and pleiotropy.

Main Results:

• The primary IVW analysis, along with all sensitivity analyses, indicated no statistically significant evidence of a causal effect of milk fat content on CKD risk.
• Minimal heterogeneity was detected among the genetic instrumental variables.
• The genetic association between self-reported milk type and CKD may reflect broader dietary patterns or genetic factors like lactose tolerance.

Conclusions:

• This study provides no support for a genetic causal link between milk fat intake and chronic kidney disease.
• The findings suggest that genetic predisposition to milk fat consumption does not directly influence CKD risk.
• Further research may be needed to clarify the complex interplay between specific dietary components, genetics, and CKD etiology.