A Bidirectional Causal Relationship between Headache and IgA Nephropathy: Evidence from a Genetic Study

Background : Pain, a major clinical, social and economic problem, has often been regarded as a symptom that serves as a warning signal of an underlying disease process. And patients with IgA nephropathy (IgAN) frequently present with region-specific pain. Therefore, this study aimed to investigate the causal relationships between region-specific pain and IgAN using a bidirectional Mendelian randomization (MR) approach. Methods : We conducted bidirectional MR analyses using genome-wide association study (GWAS) summary statistics. In the absence of heterogeneity (Cochran’s Q > 0.05), the fixed-effect inverse variance weighted (IVW) method was employed for MR analysis. Conversely, the random-effects IVW approach was applied. Furthermore, the weighted median method served as a supplementary approach. And the MR-Egger method was utilized to address horizontal pleiotropy. Results : We found a potential causal relationship: headache (OR = 2.600, 95% CI: 1.098-6.158, P = 0.030) was significantly correlated with IgAN in the forward MR analyses between region-specific pain and IgAN. And we also found a potential causal relationship between IgAN and headache (OR = 1.013, 95% CI: 1.002-1.025, P = 0.021) in the reverse MR analysis. Conclusion : s: Our study confirmed that headache can serve as an important clinical indicator for IgAN. On one hand, headaches may contribute to the pathogenesis of IgAN; on the other hand, IgAN can also precipitate headache, thereby establishing a vicious cycle that potentiates IgAN progression.