No evidence of a genetic causal relationship between ankylosing spondylitis and iron homeostasis: A two-sample Mendelian randomization study.

Abstract

Ankylosing spondylitis (AS) is an immune-mediated chronic inflammatory disease that leads to bone hyperplasia and spinal ankylosis. Iron homeostasis plays a very important role in the inflammatory response and is closely related to the pathogenesis of AS. This study aimed to use large-scale genome-wide association study (GWAS) summary data to study the genetic causal relationship between AS and iron homeostasis using Mendelian randomization (MR). Genome-wide association study summary data of AS and iron homeostasis-related indicators were obtained from the FinnGen consortium and the DeCODE genetics database, respectively. We used four iron homeostasis-related indicators: ferritin, serum iron, total iron binding capacity (TIBC), and transferrin saturation (TSAT) for two-sample MR analyses to test for genetic causal association with AS using the "TwoSampleMR" package of the R software (version 4.1.2). The random-effects inverse variance weighted (IVW) method was the main analysis method used for MR. We examined the MR analysis results for heterogeneity, horizontal pleiotropy, and possible outliers. In addition, we confirmed the robustness of the MR analysis by testing whether the results were affected by a single SNP and whether they followed a normal distribution. The random-effects IVW results showed that ferritin [p = 0.225, OR 95% confidence interval (CI) = 0.836 (0.627-1.116)], serum iron [p = 0.714, OR 95% CI = 0.948 (0.714-1.260)], TIBC [p = 0.380, OR 95% CI = 0.917 (0.755-1.113)], and TSAT [p = 0.674, OR 95% CI = 0.942 (0.713-1.244)] have no genetic causal relationship with AS. We detected no heterogeneity，horizontal pleiotropy and possible outliers in our MR analysis (p > 0.05). In addition, our MR analysis results were not affected by a single SNP, and were normally distributed. Our study did not detect a genetic causal relationship between AS and iron homeostasis. Nonetheless, this does not rule out a relationship between the two at other mechanistic levels.