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Causality between diabetes and membranous nephropathy: Mendelian randomization

Zhihang Su1, Ziqi Luo2, Di Wu1

  • 1Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 3002 Sungang West Road, Shenzhen, 518000, China.

Clinical and Experimental Nephrology
|October 7, 2024
PubMed
Abstract

Insights

This Mendelian randomization study found that various types of diabetes, including type 2, gestational, and type 1 diabetes, increase the risk of membranous nephropathy (MN). The research clarifies the causal link between diabetes and MN.

Area of Science:

  • Nephrology
  • Endocrinology
  • Genetics

Background:

  • The relationship between diabetes mellitus and membranous nephropathy (MN) requires further clarification.
  • This study investigates the causal link between multiple diabetes subtypes and MN.

Purpose of the Study:

  • To evaluate the causal effect of various diabetes types on the risk of developing membranous nephropathy (MN).
  • To summarize evidence from a Mendelian randomization (MR) study to understand the diabetes-MN association.

Main Methods:

  • Utilized genome-wide association study (GWAS) data for MN and diabetes-related traits (fasting glucose, insulin, HbA1c) from large cohorts.
  • Employed Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO methods for Mendelian randomization analysis.
  • Conducted reverse MR analysis and meta-analysis to confirm findings and assess heterogeneity and pleiotropy.

Main Results:

  • Established a causal link where type 2 diabetes, gestational diabetes, type 1 diabetes (with/without complications), maternal diabetes, and insulin use increase MN risk.
  • Found no significant association between genetically predicted fasting insulin, fasting blood glucose, or HbA1c levels and MN risk.
  • Confirmed no significant heterogeneity, horizontal pleiotropy, or reverse causality.

Conclusions:

  • Mendelian randomization analysis confirms associations between multiple diabetes subtypes and membranous nephropathy.
  • Provides enhanced understanding of the pathogenic mechanisms linking diabetes and MN.
Keywords:
DiabetesMembranous nephropathyMendelian randomizationMeta-analysis

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