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Causal association between cardiovascular proteins and membranous nephropathy: a bidirectional Mendelian

Qiqi Ma1, Gaosi Xu2

  • 1Department of Nephrology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang, 330006, Jiangxi, People's Republic of China.

International Urology and Nephrology
|March 17, 2024
PubMed

Insights

This study identifies specific cardiovascular proteins linked to membranous nephropathy (MN) risk. Findings suggest novel biomarkers for early MN detection and potential secondary disease risk identification.

Area of Science:

  • Cardiovascular Medicine
  • Nephrology
  • Genetics

Background:

  • Circulating proteins play roles in various human diseases.
  • The relationship between cardiovascular proteins and membranous nephropathy (MN) is not well understood.

Purpose of the Study:

  • To investigate the causal association between ninety cardiovascular proteins and membranous nephropathy (MN) using a bidirectional Mendelian randomization analysis.

Main Methods:

  • Bidirectional Mendelian randomization (MR) analysis utilizing genome-wide association study (GWAS) data from European populations.
  • Inverse variance weighted (IVW) method as the primary analysis, supplemented by MR-Egger, weighted median, weighted mode, and simple mode.
  • Sensitivity analyses including Cochrane's Q test, MR-Egger, and MR-PRESSO to assess pleiotropy and heterogeneity.

Main Results:

  • Fatty acid-binding protein and thrombomodulin (TM) were identified as risk factors for MN.
  • Tissue-type plasminogen activator showed a protective role against MN.
  • MN was associated with altered levels of multiple proteins including macrophage colony-stimulating factor 1, stem cell factor, and beta-nerve growth factor, with no significant pleiotropy or heterogeneity detected.

Conclusions:

  • This is the first study to establish a causal link between cardiovascular proteins and MN.
  • Identified cardiovascular proteins may serve as novel biomarkers for MN and aid in predicting secondary disease risks.
  • Further clinical validation is recommended to confirm these findings.
Abstract

Keywords:
Cardiovascular proteinsGenome-wide association studyMembranous nephropathyMendelian randomization

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