ProblemPreeclampsia, a multifaceted condition during pregnancy characterized by hypertension and organ dysfunction, poses significant risks to both maternal and fetal health. This study aims to investigate the bidirectional causal relationship between peripheral immune cell phenotypes and preeclampsia using a two‐sample Mendelian randomization (MR) approach.Method of studyGenetic data from two sizable cohorts were utilized: 3757 individuals from Sardinia, providing information on 731 immune traits, and 200 929 Finnish adult females, encompassing 6663 preeclampsia cases. Single‐nucleotide polymorphisms served as instrumental variables. The MR analyses employed the inverse variance‐weighted (IVW) method as the primary tool, supplemented by MR‐Egger, weighted median, and weighted mode methods to enhance reliability and address potential heterogeneity and horizontal pleiotropy.ResultsAmong the 731 immune cell phenotypes studied, 18 displayed a suggestive positive association (IVW p < .05) with heightened preeclampsia risk, while 20 exhibited a suggestive negative association linked to reduced risk. Following false discovery rate (FDR) adjustment, four immune phenotypes showed significant associations with decreased preeclampsia risk: CD27 on CD24+ CD27+ B cells (B‐cell panel) (odds ratio [OR] = 0.927, PFDR = 0.061), CD33+ HLA DR+ CD14− absolute count (OR = 0.963, PFDR = 0.061), CD80 on plasmacytoid dendritic cells (OR = 0.923, PFDR = 0.061); and CD80 on CD62L+ plasmacytoid dendritic cells (OR = 0.923, PFDR = 0.061). In the reverse‐direction MR analysis, no significant causal effects of preeclampsia on immune cell phenotypes were observed.ConclusionsThis study provides quantifiable evidence linking specific immune cell phenotypes to the risk of developing preeclampsia. This novel understanding of the immunological aspects underlying preeclampsia's pathogenesis could lead to innovative therapeutic strategies centered on immune modulation.

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研究广泛的外周免疫细胞表型与先兆子痫之间的因果关系：双向孟德尔随机分析

问题先兆子痫是妊娠期间的一种多方面疾病，其特征是高血压和器官功能障碍，对母亲和胎儿的健康构成重大风险。本研究旨在使用双样本孟德尔随机化 (MR) 方法研究外周免疫细胞表型与先兆子痫之间的双向因果关系。研究方法利用了两个相当大的队列的遗传数据：来自撒丁岛的 3757 名个体，提供了 731 种免疫特征的信息，以及 200929 名芬兰成年女性，其中包括 6663 例先兆子痫病例。单核苷酸多态性作为工具变量。 MR 分析采用逆方差加权 (IVW) 方法作为主要工具，辅以 MR-Egger、加权中位数和加权模式方法，以增强可靠性并解决潜在的异质性和水平多效性。结果在研究的 731 个免疫细胞表型中， 18 显示出暗示性正相关（IVWp< .05) 与先兆子痫风险升高有关，而 20 则表现出与风险降低相关的暗示性负相关。错误发现率 (FDR) 调整后，四种免疫表型显示与先兆子痫风险降低显着相关：CD24+ CD27+ B 细胞（B 细胞组）上的 CD27（比值比 [OR] = 0.927，P罗斯福= 0.061), CD33+ HLA DR+ CD14− 绝对计数 (OR = 0.963, P罗斯福= 0.061), 浆细胞样树突状细胞上的 CD80 (OR = 0.923, P罗斯福= 0.061);和 CD62L+ 浆细胞样树突状细胞上的 CD80（OR = 0.923，P罗斯福= 0.061）。在反向 MR 分析中，没有观察到先兆子痫对免疫细胞表型的显着因果影响。结论本研究提供了将特定免疫细胞表型与发生先兆子痫的风险联系起来的量化证据。这种对先兆子痫发病机制的免疫学方面的新认识可能会导致以免疫调节为中心的创新治疗策略。