儿童期体重指数及出生体重与未来妊娠期高血压及子痫前期-子痫因果关系的两样本孟德尔随机化研究

The Potential Association of Childhood Body Mass Index and Birth Weight With Future Gestational Hypertension and Preeclampsia-eclampsia:a Mendelian Randomization Study

目的:应用两样本孟德尔随机化(MR)方法探讨儿童期体重指数及出生体重与未来妊娠期高血压及子痫前期-子痫之间的因果联系。方法:以单核苷酸多态性(SNP)为工具变量,从全基因组关联分析数据中筛出与儿童期体重指数及出生体重相关的SNP,用MR Egger回归法、逆方差加权法(IVW)和加权中位数法3种两样本MR方法分析儿童期体重指数及出生体重与未来妊娠期高血压及子痫前期-子痫之间的因果关联。结果:随着儿童体重指数增加,未来妊娠期高血压(IVW的随机效应模型:OR=1.417,95%CI:1.144~1.755,P=0.001;加权中位数法:OR=1.277,95%CI:1.028~1.587,P=0.027)和子痫前期-子痫(IVW:OR=1.399,95%CI:1.130~1.733,P=0.002)发病风险均增加。出生体重与未来妊娠期高血压及子痫前期-子痫之间的因果关联无统计学意义(P均>0.05)。敏感性分析支持上述因果关联的稳健性。结论:儿童期体重指数与未来妊娠期高血压及子痫前期-子痫之间存在正向因果关联。出生体重与未来妊娠期高血压及子痫前期-子痫之间的因果关联无统计学意义。

Objectives:To explore the potential association of childhood body mass index(BMI)and birth weight with future gestational hypertension and preeclampsia-eclampsia using two-sample Mendelian randomization(MR)analysis.Methods:Single nucleotide polymorphisms(SNP)were used as instrumental variables and SNP associated with childhood BMI and birth weight were selected from genome-wide association studies(GWAS)data.MR Egger regression,inverse variance weighting(IVW)and weighted median methods were used to investigate the potential association of childhood body mass index and birth weight with future gestational hypertension and preeclampsia-eclampsia.Results:The risk of future gestational hypertension(the multiplicative random effects IVW:OR=1.417,95%CI:1.144-1.755,P=0.001;weighted median:OR=1.277,95%CI:1.028-1.587,P=0.027)and preeclampsia-eclampsia(IVW:OR=1.399,95%CI:1.130-1.733,P=0.002)increased with increasing BMI in childhood.There was no association between genetically proxied birth weight and future gestational hypertension and preeclampsia-eclampsia.Sensitivity analysis supported the robustness of the defined association.Conclusions:There is a positive association of childhood body mass index with future gestational hypertension and preeclampsia-eclampsia.