Gene prediction of the relationship between iron deficiency anemia and immune cells

Observational studies have shown a potential link between immune factors and the risk of iron deficiency anemia (IDA), yet the causal relationship between immune cells and IDA remains enigmatic. Herein, we used Mendelian randomization (MR) to assess whether this association is causal. We selected IDA genetic variants, including 8376 samples and 9810691 single nucleotide polymorphisms, and immune cells from a large open genome-wide association study (GWAS) for a bidirectional MR study. The primary method was inverse variance weighting (IVW), and auxiliary analyses were MR-Egger, weighted median, simple mode and weighted mode. The reliability of the results was subsequently verified by heterogeneity and sensitivity analysis. IVW method showed that 19 types of immune cells may be the risk factors of IDA, whereas 15 types of immune cells are the protective factors of IDA. Reverse MR analysis suggested that immune cells from upstream etiology of IDA are not involved in follow-up immune activities. Next, we selected 731 immune cell types as the results. The research revealed that IDA may result in a rise in 23 kinds of immune cells and a reduction in 12 kinds of immune cells. In addition, sensitivity analysis demonstrated no evidence of heterogeneity or horizontal pleiotropy. From a genetic standpoint, our study suggests that specific immune cells may be involved in the occurrence of IDA. Inversely, IDA may also contribute to immune dysfunction, thus guiding future clinical investigations.

观察性研究已揭示免疫因素与缺铁性贫血（iron deficiency anemia, IDA）风险之间存在潜在关联，但免疫细胞与IDA之间的因果关系仍待阐明。为此，我们采用孟德尔随机化（Mendelian randomization, MR）方法评估该关联是否具有因果性。我们选取了IDA相关基因变异数据（包含8376个样本及9810691个单核苷酸多态性（single nucleotide polymorphism）），并从大型公开全基因组关联研究（genome-wide association study, GWAS）中获取免疫细胞数据，开展双向MR研究。主要分析方法为逆方差加权法（inverse variance weighting, IVW），辅助分析方法包括MR-Egger、加权中位数法、简单模式法及加权模式法。随后通过异质性分析与敏感性分析验证结果的可靠性。IVW结果显示，19种免疫细胞可能是IDA的风险因素，而15种免疫细胞为IDA的保护因素。反向MR分析提示，IDA上游病因相关的免疫细胞未参与后续免疫活动。接下来，我们选取731种免疫细胞类型进一步分析，发现IDA可能导致23种免疫细胞数量上升、12种数量下降。此外，敏感性分析未发现异质性或水平多效性的证据。从遗传学角度，本研究提示特定免疫细胞可能参与IDA的发生；反之，IDA也可能导致免疫功能障碍，从而为未来临床研究提供指导。