欧洲人群中Graves病对妊娠期高血压风险的因果影响:基于孟德尔随机化方法的机制分析

Causal effect of Graves disease on risk of hypertensive disorders during pregnancy in European: a mechanistic analysis based on Mendelian randomization

摘要

目的 本研究旨在通过孟德尔随机化(MR)分析,探讨毒性弥漫性甲状腺肿(Graves)病对妊娠期高血压疾病的因果影响,并揭示其潜在的生物学机制。方法 本研究从芬兰生物银行(FinnGen)获得妊娠期高血压数据,从IEU open GWAS数据库获取Graves病遗传变异数据,采用四种孟德尔随机化统计方法(逆方差加权法、MR-Egger法、加权中位数法、加权模式法)对Graves病与妊娠期高血压的因果关系进行分析.使用与Graves病相关的单核苷酸多态性(SNP)作为工具变量,以减少混杂因素和反向因果关系的影响。结果 本研究共得到25个符合MR假设的工具变量.逆方差加权法分析显示Graves病降低了妊娠期高血压疾病的发生风险(OR=0.951,95%CI:0.926~0.976,P=0.001).MR-Egger(OR=0.927,95%CI:0.861~0.998)、加权中位数法(OR=0.943,95%CI:0.909~0.977)和加权模式法(OR=0.938,95%CI:0.899~0.979)的结果均支持这一结论(均P<0.05).Cochran's Q检验显示纳入的SNPs存在异质性,异质性为4.377%(Q=24.536,P=0.375).研究纳入的25个工具变量均为强工具变量,SNP的F值均>10(30.42~306.74)。结论 本研究通过孟德尔随机化方法显示,欧洲人群中Graves病降低了妊娠期高血压疾病的发生风险.

Abstract

Objective This study aims to investigate the causal effect of toxic diffuse goiter (Graves' disease) on hypertensive disorders during pregnancy (HDP) through Mendelian randomization (MR) analysis and to elucidate its potential biological mechanisms. Methods This study obtained data on hypertensive disorders during pregnancy from the Finnish Biobank (FinnGen) and genetic variation data for Graves' disease from the IEU Open GWAS database. We employed four MR statistical methods including Inverse-Variance Weighted (IVW), MR-Egger, Weighted Median, and Weighted Mode to analyse the causal relationship between Graves' disease and HDP during pregnancy. Single nucleotide polymorphisms (SNPs) associated with Graves' disease were used as instrumental variables to minimize the influence of confounding factors and reverse causality. Results A total of 25 instrumental variables consistent with the MR assumptions were identified in this study. The IVW analysis showed that Graves' disease reduced the risk of HDP during pregnancy (OR=0.951, 95%CI: 0.926-0.976, P=0.001). The results from MR-Egger (OR=0.927, 95%CI: 0.861-0.998), Weighted Median (OR=0.943, 95%CI: 0.909-0.977), and Weighted Mode (OR=0.938, 95%CI: 0.899-0.979) all supported this conclusion (all P<0.05). Cochran's Q test indicated heterogeneity among the included SNPs, with heterogeneity at 4.377% (Q=24.536, P=0.375). All 25 instrumental variables used in the study were strong instruments, with SNP F-values >10 (ranging from 30.42 to 306.74). Conclusion This study using Mendelian randomization demonstrates that Graves' disease reduces the risk of hypertensive disorders during pregnancy in European populations.

关键词

Graves病 / 妊娠期高血压 / 孟德尔随机化 / 因果关系 / 欧洲人群

Key words

Graves' disease / hypertensive disorders of pregnancy / Mendelian randomization / causal relationship / European population

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