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Exploring the potential causal association between genetic factors for multiple sclerosis and genetic factors for

Shaoyi Peng1, Kaiyuan Li2,3, Lingyu Han3

  • 1Department of Cardiology, Jiande First People's Hospital, Hangzhou, China.

Medicine
|July 23, 2025
PubMed

Insights

Genetic susceptibility to multiple sclerosis (MS) increases nephrotic syndrome risk but lowers diabetic nephropathy risk. This research explores the genetic links between MS and kidney diseases, aiding clinical assessments.

Area of Science:

  • Immunogenetics
  • Nephrology
  • Neurology

Background:

  • The relationship between genetic factors for multiple sclerosis (MS) and kidney disease risk is not well understood.
  • Clarifying this association can offer insights into comorbidity and enhance clinical risk evaluations.

Purpose of the Study:

  • To investigate the potential causal link between genetic susceptibility to MS and the risk of various kidney diseases.
  • To explore shared immunogenetic pathways between MS and renal conditions.

Main Methods:

  • A two-sample Mendelian randomization analysis was performed using genome-wide association study data.
  • Single nucleotide polymorphisms associated with MS served as instrumental variables for analyzing outcomes like nephrotic syndrome, glomerulonephritis, tubulointerstitial nephritis, and diabetic nephropathy.
  • Statistical methods included inverse variance weighted, MR-Egger, and weighted median approaches, with assessments for pleiotropy and heterogeneity.

Main Results:

  • Genetic predisposition to MS showed a positive association with an increased risk of nephrotic syndrome (OR=1.14, P=0.009).
  • Conversely, MS genetic liability was linked to a reduced risk of diabetic nephropathy (OR=0.83, P=0.006).
  • No significant causal associations were identified for glomerulonephritis or tubulointerstitial nephritis. Sensitivity analyses confirmed the robustness of the findings.

Conclusions:

  • Genetic factors predisposing individuals to MS may elevate the risk for nephrotic syndrome while concurrently decreasing the risk for diabetic nephropathy.
  • These findings suggest underlying shared immunogenetic mechanisms connecting MS and specific kidney diseases.
  • The results underscore the importance of renal health monitoring in the management of multiple sclerosis patients.
Keywords:
Mendelian randomization studydiabetic nephropathymultiple sclerosisnephrotic syndromesingle nucleotide polymorphisms

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