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肺功能的孟德尔随机化证据介导了儿童期过敏(年龄<16岁)与原发性高血压之间的关联。

Mendelian randomization evidence for lung function mediates the association between childhood allergies (age <16 years) and essential hypertension.

作者信息

Long Yu-Hang, She Jun-Sen, Guo Fei, Zhou Bo-Kang, Fang Chen, Hu Yi-Zhi, Gao Ling, Huang He-Feng

机构信息

Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai 200011, China.

International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, China.

出版信息

Reprod Dev Med. 2025 Mar;9(1):48-56. doi: 10.1097/RD9.0000000000000121. Epub 2024 Dec 17.

Abstract

OBJECTIVE

This study aimed to investigate the influence of lung function on the relationship between allergies and hypertension, thereby elucidating significant potential mechanisms from a genetic standpoint. We investigated the causal relationship between childhood allergies (age <16 years) and essential hypertension and identified and quantified the role of lung function (forced vital capacity [FVC] and forced expiratory volume in the first second/forced vital capacity [FEV1/FVC]) as potential mediators.

METHODS

Using data from a genome-wide association study and the Fenn Genn consortium, a two-sample Mendelian randomization (MR) analysis of genetically predicted childhood allergies (7128 cases and 211,703 controls) and essential hypertension (116,714 cases and 1,032,659 controls) was performed. Furthermore, we used two-step MR to quantify the effect of lung function-mediated childhood allergies on essential hypertension. The FVC and FEV1/FV sample size was 371,898.

RESULTS

Childhood allergies were associated with increased odds of developing essential hypertension (odds ratio [] = 1.0900, 95% confidence interval [] = 1.0034-1.1842,  = 0.0414). No strong evidence that genetically predicted essential hypertension affected childhood allergy risk was identified ( = 1.0631, 95%  = 0.9829-1.1498,  = 0.1264). The proportion of genetically predicted childhood allergies mediated only by FVC was 5.67% (95% , 5.13%-5.73%).

CONCLUSION

A causal relationship between childhood allergies and essential hypertension was identified, with a proportion of the effect mediated by FVC. Therefore, implementing early interventions in children with allergies is imperative to mitigate the long-term risk of developing hypertension. Further research is required to identify additional risk factors as potential mediators.

摘要

目的

本研究旨在探讨肺功能对过敏与高血压之间关系的影响,从而从遗传学角度阐明潜在的重要机制。我们研究了儿童期过敏(年龄<16岁)与原发性高血压之间的因果关系,并确定和量化了肺功能(用力肺活量[FVC]和第一秒用力呼气量/用力肺活量[FEV1/FVC])作为潜在中介因素的作用。

方法

利用全基因组关联研究和芬兰基因组联盟的数据,对基因预测的儿童期过敏(7128例病例和211,703例对照)和原发性高血压(116,714例病例和1,032,659例对照)进行了两样本孟德尔随机化(MR)分析。此外,我们采用两步MR法量化肺功能介导的儿童期过敏对原发性高血压的影响。FVC和FEV1/FV的样本量为371,898。

结果

儿童期过敏与发生原发性高血压的几率增加相关(优势比[] = 1.0900,95%置信区间[] = 1.0034 - 1.1842, = 0.0414)。未发现基因预测的原发性高血压影响儿童期过敏风险的有力证据( = 1.0631,95%  = 0.9829 - 1.1498, = 0.1264)。仅由FVC介导的基因预测儿童期过敏的比例为5.67%(95% ,5.13% - 5.73%)。

结论

确定了儿童期过敏与原发性高血压之间的因果关系,部分影响由FVC介导。因此,对过敏儿童实施早期干预以降低发生高血压的长期风险势在必行。需要进一步研究以确定其他风险因素作为潜在中介因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3ef/11949214/8d11a4093e76/rd9-9-48-g001.jpg

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