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

Abstract

Background There is a close clinical association between hypothyroidism and nephrotic syndrome (NS) was close, but whether there is genetic causality between the two is not known.Objective Using pooled data from a genome-wide association study (GWAS), the association between hypothyroidism and NS was explored via Mendelian randomization (MR) analysis.Methods Single-nucleotide polymorphisms (SNPs) associated with hypothyroidism (or NS) were screened as genetic instrumental variables (IVs) from pooled GWAS data, and inverse-variance weighting (IVW) was used for the main analysis to estimate causal effects, with MR-Egger, weighted median, and weighted mode used as complementary methods. Sensitivity analyses, including Cochran’s Q test, MR-Egger intercept, MR-PRESSO and leave-one-out, were also conducted to assess the robustness of the results.Results Genetically predicted hypothyroidism was positively associated with the risk of developing NS (IVW: OR = 1.18, 95% CI: 1.07–1.30, p = 0.00; MR-Egger: OR = 1.36, 95% CI: 1.10–1.68, p = 0.01), and the MR-Egger intercept (intercept = −0.02, p = 0.14), MR-PRESSO test (p = 0.14), Cochran’s Q test (p = 0.15) and leave-one-out test results supported the robustness of the results. Genetically predicted NS status might not be associated with an increased risk of developing hypothyroidism (IVW: OR = 1.01, 95% CI: 1.00–1.03, p = 0.08; MR-Egger: OR = 1.01, 95% CI: 0.98–1.04, p = 0.43), and the MR-Egger intercept (intercept < 0.01, p = 0.69), MR-PRESSO test (p = 0.64), Cochran’s Q test (p = 0.61) and leave-one-out test results supported the robustness of the results.Conclusion Hypothyroidism status could increase the risk of developing NS.

Keywords

• hypothyroidism
• nephrotic syndrome
• Mendelian randomization
• genome-wide association study