免疫表型与妊娠糖尿病的因果关联：基于孟德尔 随机化分析

打开文本图片集

【中图分类号】R714.256 【文献标识码】A

Exploring the causal association of immunophenotypes on gestational diabetes mellitus based on Mendelian randomization

WANG Juan1，WANG Qiong²，LIN Xingguang³，YE Xiaohe1， SHEN Li1

1. Department of Obstetricsand Gynecology， Liyuan Hospital， Tongji Medical Collge，Huazhong

Universityof Scienceand Technology，Wuhan 43o077，China

2. Department ofObstetrics and Gynecology， Chongyang Maternal and Child Health Hospital， Xianning

437500，Hubei Province， China

3.Department of Obstetrics and Gynecology， Tongji hospital， Tongji Medical Collge，Huazhong

UniversityofScienceandTechnology，Wuhan43oo3o，China

Corresponding author： SHEN Li， Email： shenghuoys123@sina.com

【Abstract】 Objective To explore the causal relationship between immune cell phenotypes and the risk of developing gestational diabetes melitus （GDM） by using Mendelian randomization （MR）. Methods Using genome-wide association study data from European populations， we extracted 731 immune cel traits as instrumental variables，and obtained GDM summary statistics from the Finnish database （FinnGen）.The inverse-variance weighted （IVW） method served as the primary estimator， supplemented by the weighted median，MR-Egger regression，simple mode，and weighted mode to evaluate the causal relationship between immune cellphenotypes and GDM， with additional tests for heterogeneity， horizontal pleiotropy，and sensitivity analyses. Reverse MR was further conducted to asses the potential causal impact of GDM on immune phenotypes. Results A total of 40 immune phenotypes showed potential causal associations with GDM risk.After false discovery rate correction （ FDR<0.05 ），two phenotypes remained significant： HLA DR on CD33-HLA DR+ [OR ：=1.107 ， 95%CI （1.050，1.166）] and HLA DR on DC OR=1.098 ， 95%CI （1.048，1.150）]. Reverse MR revealed no significant causal impact of GDM on any of the 40 immune phenotypes （P>0.05） . Conclusion Specific immune cell phenotypes （HLA DR on CD33- HLA DR+ ，HLADR on DC）maybe potential causal risk factors for the development of GDM and may provide targets for future risk prediction and immune intervention strategies.

【KeyWords】 Gestational diabetes mellitus; Immune cell phenotype; Mendelian randomization Genome-wide association study; Causality

妊娠糖尿病（gestational diabetesmellitus，GDM）是一种常见的孕期代谢紊乱，其发病率呈上升趋势[]。（剩余14589字）