Study Highlights Causal Effect of High Blood Pressure, Triglycerides on IgA Nephropathy

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High blood pressure and triglycerides may be important risk factors for IgA nephropathy (IgAN), according to findings from a recent Mendelian randomization analysis.¹

Although both high blood pressure and triglycerides were identified as risk factors, high blood pressure had a more significant influence on disease onset and was more strongly causally linked to IgAN.¹

“Results [from previous research] indicate that both triglycerides and high blood pressure have strong correlations with IgAN,” Yijun Yang, of the First Affiliated Hospital of Xi’an Jiaotong University in China, and colleagues wrote.¹ “However, it is still unclear whether there is a direct causal effect of triglycerides and high blood pressure on IgAN.”

Hyperlipidemia and high blood pressure are common complications of renal dysfunction in IgAN. Although its exact cause is unknown, recent research suggests both high blood pressure and triglycerides may play a causal role in IgAN.²

To explore the causal effect of high blood pressure and triglycerides on IgAN, investigators sourced genome-wide association study (GWAS) summary data from the GWAS Catalog and Integrative Epidemiology Unit OpenGWAS databases. After selecting single nucleotide polymorphisms (SNPs) as instrumental variables, investigators performed Mendelian randomization analysis with MR-Egger, weighted median, simple mode, weighted mode, and inverse variance weighted methods.¹

Investigators also conducted a sensitivity analysis with heterogeneity, horizontal pleiotropy test, and leave-one-out analysis. Additionally, in order to explore the biological function and signal pathway of the relevant genes regulated by SNPs, investigators obtained the genes corresponding to SNPs related to triglycerides and high blood pressure and performed enrichment analysis and interaction network construction.¹

Univariate Mendelian randomization results revealed high blood pressure (Odds ratio [OR], 1.970; 95% CI, 1.507–2.575; P = 7.09 × 10−7) and triglycerides (OR, 1.065; 95% CI, 1.001–1.133; P = .046) regarded as risk factors were causally related to IgAN based on the random-effect inverse variance weighted method. In this analysis, investigators noted triglycerides had a weaker impact.¹

The reliability of these results was confirmed in a sensitivity analysis, which showed no horizontal pleiotropy and exaggerated influence of each SNP, thus confirming triglycerides and high blood pressure were risk factors in causal connection with IgAN.¹

In multivariate Mendelian randomization analysis, triglycerides (OR, 1.032; 95% CI, 0.968–1.101) and high blood pressure (OR, 1.731; 95% CI, 1.270–2.360) remained risk factors for IgAN. However, investigators noted only high blood pressure was causally related to IgAN (P = .000512) and was deemed to have direct influence on IgAN when occurring simultaneously with triglycerides.¹

A total of 208 and 153 genes separately corresponding to SNPs of triglycerides and high blood pressure, respectively, were included in enrichment analysis. Investigators pointed out genes relevant to triglycerides were mainly enriched in lipid homeostasis and cholesterol metabolism, while genes concerned with high blood pressure played their roles in regulation of cell growth, aldosterone synthesis, and secretion.¹

Investigators highlighted multiple limitations to these findings, including the lack of consideration for other influencing factors in IgAN, the impact of gender and age on exposure factors and outcomes assessed in the study, and variations in IgAN incidence by region.¹

“In conclusion, there is a causal effect of triglycerides and high blood pressure on IgAN, both of them are risk factors, and high blood pressure is the direct influencing factor of IgAN,” investigators wrote.¹

References:

1. ^{Yang Y, Li Y, Feng X, et al. The causal effect of triglyceride and high blood pressure on IgA nephropathy: a Mendelian randomization study. Front Med (Lausanne). 2024;11:1338462. doi:10.3389/fmed.2024.1338462}
2. ^{NIDDK. IgA Nephropathy. Kidney Disease. September 2022. Accessed March 22, 2024. https://www.niddk.nih.gov/health-information/kidney-disease/iga-nephropathy}