METHODS: We performed bidirectional two-sample Mendelian randomization (2SMR) to investigate the causal connection between circulating inflammatory cytokines and gestational diabetes mellitus. Publicly accessible data for circulating inflammatory cytokines (8,293 individuals) and gestational diabetes mellitus (123,579 individuals) were obtained from genome-wide association study (GWAS).
RESULTS: Only one causal association was identified between circulating inflammatory cytokines and GDM. The inverse variance weighting (IVW) method showed that macrophage migration inhibitory factor (MIF) increased the risk of GDM (OR 1.162, 95%CI 1.044,1.293). Moreover, two causal associations were detected between GDM and circulating inflammatory cytokines. GDM was negatively correlated with interferon gamma-induced protein 10 (IP10) (Beta -0.129, 95%CI -0.236,-0.231) and interleukin-18 (IL18) (Beta -0.133, 95%CI -0.241,-0.026).
CONCLUSIONS: Mendelian randomization study revealed MIF as a risk factor for gestational diabetes mellitus. This finding offers a new and valuable insight into the pathophysiological mechanisms underlying GDM.
方法:我们进行了双向双样本孟德尔随机化(2SMR),以研究循环炎性细胞因子与妊娠期糖尿病之间的因果关系。循环炎症细胞因子(8,293名个体)和妊娠糖尿病(123,579名个体)的公开数据来自全基因组关联研究(GWAS)。
结果:在循环炎性细胞因子和GDM之间仅发现一种因果关系。方差反加权(IVW)方法显示巨噬细胞移动抑制因子(MIF)增加GDM的风险(OR1.162,95CI1.044,1.293)。此外,在GDM和循环炎性细胞因子之间检测到两个因果关系.GDM与干扰素γ诱导蛋白10(IP10)(β-0.129,95CI-0.236,-0.231)和白细胞介素18(IL18)(β-0.133,95CI-0.241,-0.026)呈负相关。
结论:孟德尔随机研究显示MIF是妊娠期糖尿病的危险因素。这一发现为GDM的病理生理机制提供了新的有价值的见解。