Yang Mingyi, Yu Hui, Xu Ke, Xie Jiale, Zheng Haishi, Feng Ruoyang, Wang Jiachen, Xu Peng
Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Front Nutr. 2023 Mar 23;10:1047640. doi: 10.3389/fnut.2023.1047640. eCollection 2023.
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 [ = 0.225, OR 95% confidence interval (CI) = 0.836 (0.627-1.116)], serum iron [ = 0.714, OR 95% CI = 0.948 (0.714-1.260)], TIBC [ = 0.380, OR 95% CI = 0.917 (0.755-1.113)], and TSAT [ = 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 ( > 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.
强直性脊柱炎（AS）是一种免疫介导的慢性炎症性疾病，可导致骨质增生和脊柱强直。铁稳态在炎症反应中起非常重要的作用，且与AS的发病机制密切相关。本研究旨在利用大规模全基因组关联研究（GWAS）汇总数据，采用孟德尔随机化（MR）方法研究AS与铁稳态之间的遗传因果关系。
分别从芬兰基因联盟（FinnGen consortium）和迪科德遗传学数据库（DeCODE genetics database）获取AS和铁稳态相关指标的全基因组关联研究汇总数据。我们使用四个与铁稳态相关的指标：铁蛋白、血清铁、总铁结合力（TIBC）和转铁蛋白饱和度（TSAT）进行两样本MR分析，以使用R软件（版本4.1.2）的“TwoSampleMR”包检验与AS的遗传因果关联。随机效应逆方差加权（IVW）方法是用于MR的主要分析方法。我们检查了MR分析结果的异质性、水平多效性和可能的异常值。此外，我们通过测试结果是否受单个单核苷酸多态性（SNP）影响以及是否呈正态分布来确认MR分析的稳健性。
随机效应IVW结果显示，铁蛋白[β = 0.225，比值比（OR）95%置信区间（CI）= 0.836（0.627 - 1.116）]、血清铁[β = 0.714，OR 95% CI = 0.948（0.714 - 1.260）]、TIBC[β = 0.380，OR 95% CI = 0.917（0.755 - 1.113）]和TSAT[β = 0.674，OR 95% CI = （0.713 - 1.244）]与AS无遗传因果关系。我们在MR分析中未检测到异质性、水平多效性和可能的异常值（P > 0.05）。此外，我们的MR分析结果不受单个SNP影响，且呈正态分布。
我们的研究未检测到AS与铁稳态之间的遗传因果关系。尽管如此，这并不排除两者在其他机制水平上的关系。
