Association between hypothyroidism and nephrotic syndrome: a bidirectional two-sample Mendelian randomization...

Area of Science:

• Genetics
• Epidemiology
• Endocrinology

Background:

• A clinical association exists between hypothyroidism and nephrotic syndrome (NS).
• The genetic causality between hypothyroidism and NS remains unestablished.
• Understanding this relationship is crucial for clinical management and preventative strategies.

Purpose of the Study:

• To investigate the potential genetic causal relationship between hypothyroidism and nephrotic syndrome (NS).
• To utilize Mendelian randomization (MR) analysis to assess causality.
• To provide evidence for or against a direct genetic link between the two conditions.

Main Methods:

• Employed Mendelian randomization (MR) analysis using pooled genome-wide association study (GWAS) data.
• Selected single-nucleotide polymorphisms (SNPs) associated with hypothyroidism and NS as genetic instrumental variables (IVs).
• Utilized inverse-variance weighting (IVW) for primary analysis, with MR-Egger, weighted median, and weighted mode as complementary methods. Conducted sensitivity analyses to ensure result robustness.

Main Results:

• Genetically predicted hypothyroidism showed a significant positive association with an increased risk of developing NS (IVW: OR = 1.18).
• Sensitivity analyses, including MR-Egger, MR-PRESSO, and Cochran's Q tests, supported the robustness of these findings.
• Conversely, genetically predicted NS status was not significantly associated with an increased risk of developing hypothyroidism.

Conclusions:

• Hypothyroidism status is causally linked to an increased risk of developing nephrotic syndrome (NS).
• The findings suggest a unidirectional causal effect from hypothyroidism to NS.
• This supports the importance of managing hypothyroidism to potentially mitigate NS risk.