评估母体红细胞叶酸与后代先天性心脏病的因果关系：双样本孟德尔随机化

IF 3.3 3区医学 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH

Annals of Epidemiology Pub Date : 2025-04-14 DOI:10.1016/j.annepidem.2025.04.010

Hongyan Chen , Xiaotian Chen , Qinyu Yao , Jibin Xin , Yi Zhang , Xiangyuan Huang , Dingmei Wang , Mengru Li , Tiansong Zhang , Taavi Tillmann , Weili Yan , Guoying Huang

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引用次数: 0

摘要

目的：采用两样本孟德尔随机化（MR）方法，利用母体MTHFR C677T作为遗传工具，验证母体红细胞（RBC）叶酸与后代先天性心脏病（CHD）风险之间的因果关系。方法通过两项全基因组关联研究（Trinity Student Study [n = 2229]）和上海孕前亚队列研究[n = 980])的数据汇总，获得红细胞叶酸的遗传关联。我们对遗传研究进行了荟萃分析，以获得冠心病的相关性(35项研究；结果母体MTHFR C677T变异与较低的红细胞叶酸（每个风险等位基因-116 nmol/L）和较高的冠心病风险相关(优势比[OR]， 1.32 /等位基因；95 % ci, 1.18-1.47)。每100 nmol/L基因决定较高的红细胞叶酸与冠心病风险降低21% %相关（OR, 0.79[0.70-0.90]）。这种关联在亚洲人群（0.72[0.61-0.85]）和叶酸水平低的地区（0.76[0.65-0.88]）中很明显，但在高加索人群（0.96[0.89-1.04]）和强化地区（0.92[0.79-1.06]）中不明显。结论：研究结果支持母亲叶酸水平对后代冠心病风险的因果作用，主要局限于叶酸水平较低的亚洲人群和地区。

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Appraising the causal relevance of maternal red blood cell folate and congenital heart disease in offspring: 2-sample Mendelian randomization

Purpose

We performed a 2-sample Mendelian randomization (MR) using maternal MTHFR C677T as the genetic instrument to validate the causal association between maternal red blood cell (RBC) folate and offspring congenital heart disease (CHD) risk.

Methods

We obtained the genetic association for RBC folate through pooling data from 2 genome-wide association studies (the Trinity Student Study [n = 2229]) and Shanghai Preconception sub-cohort [n = 980]). We performed a meta-analysis of genetic studies to obtain the association for CHD (35 studies; 6141 CHDs and 14078 controls) and used the Wald ratio method for the 2-sample MR.

Results

Maternal MTHFR C677T variant was associated with lower RBC folate (-116 nmol/L per risk allele) and higher CHD risk (odds ratio [OR], 1.32 per allele; 95 % CI, 1.18–1.47). Per 100-nmol/L genetically determined higher RBC folate was associated with 21 % lower CHD risk (OR, 0.79 [0.70–0.90]). The association was evident in the Asian populations (0.72 [0.61–0.85]) and regions with low folate status (0.76 [0.65–0.88]) but not in the Caucasian populations (0.96 [0.89–1.04]) or regions with fortification (0.92 [0.79–1.06]).

Conclusions

Our findings support a causal role of maternal folate in offspring CHD risk, mainly confined to Asian populations and regions with low folate status.

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来源期刊

Annals of Epidemiology 医学-公共卫生、环境卫生与职业卫生

CiteScore

7.40

自引率

1.80%

发文量

207

审稿时长

59 days

期刊介绍： The journal emphasizes the application of epidemiologic methods to issues that affect the distribution and determinants of human illness in diverse contexts. Its primary focus is on chronic and acute conditions of diverse etiologies and of major importance to clinical medicine, public health, and health care delivery.