Causal effects of female reproductive features on nonalcoholic fatty liver disease: A mendelian randomization study

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2024-09-08 DOI:10.1002/jgm.3738

Haoshuang Fu, Shuying Song, Bingying Du, Tianhui Zhou, Minghao Cai, Shaowen Jiang, Yaoxing Chen, Xinya Zang, Yan Huang, Weijing Wang, Qing Xie

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引用次数: 0

Abstract

Background and aims

Epidemiological evidence on the associations between female reproductive features and nonalcoholic fatty liver disease (NAFLD) is conflicting. To explore their causalities, we conducted a Mendelian randomization (MR) study.

Methods

Summary-level data were obtained, and univariable MR was performed to explore the causalities between female reproductive features and NAFLD. And we performed multivariable MR and MR mediation analysis to explore the mediation effects of educational attainment (EA) and body mass index (BMI) for these associations. Sensitivity analyses were performed to evaluate pleiotropy and heterogeneity.

Results

There were causal effects of age at menarche (AAMA) (odds ratio [OR]: 0.817, 95% confidence interval [CI]: 0.736–0.907, per year-increase), age at first birth (AFB) (OR: 0.851, 95%CI: 0.791–0.926, per year-increase) and age at first sexual intercourse (AFS) (OR: 0.676, 95%CI: 0.511–0.896, per standard deviation-increase) on NAFLD risk. Besides, the causal effects were also observed on NAFLD phenotypes including liver fat content (LFC) and alanine aminotransferase (ALT). Further mediation analysis showed that BMI mediated partial proportion of effects of AAMA and AFS on NAFLD/ALT, AFB on NAFLD/LFC/ALT, while EA mediated partial proportion of effects of AFB on NAFLD/LFC/ALT, and AFS on NAFLD/ALT.

Conclusions

This study provided convincing evidence that early AAMA, AFB, and AFS were risk factors for NAFLD. Reproductive health education, obesity management, and education spread might be the beneficial strategies for NAFLD prevention.

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女性生殖特征对非酒精性脂肪肝的因果效应：孟德尔随机化研究

背景和目的：关于女性生殖特征与非酒精性脂肪肝（NAFLD）之间关系的流行病学证据相互矛盾。为了探究其因果关系，我们进行了一项孟德尔随机化（MR）研究：方法：我们获得了汇总数据，并进行了单变量 MR，以探讨女性生殖特征与非酒精性脂肪肝之间的因果关系。我们还进行了多变量 MR 和 MR 中介分析，以探讨教育程度（EA）和体重指数（BMI）对这些关联的中介效应。我们还进行了敏感性分析，以评估多义性和异质性：结果：初潮年龄（AAMA）有因果效应（几率比 [OR]：0.817，95% 置信区间 [CI]：初潮年龄（AAMA）（几率比[OR]：0.817，95%置信区间[CI]：0.736-0.907，每增加一年）、初产年龄（AFB）（OR：0.851，95%置信区间：0.791-0.926，每增加一年）和初次性交年龄（AFS）（OR：0.676，95%置信区间：0.511-0.896，每增加一个标准差）对非酒精性脂肪肝风险有因果效应。此外，非酒精性脂肪肝表型（包括肝脏脂肪含量（LFC）和丙氨酸氨基转移酶（ALT））也受到因果效应的影响。进一步的中介分析表明，BMI中介了AAMA和AFS对NAFLD/ALT、AFB对NAFLD/LFC/ALT的部分影响，而EA中介了AFB对NAFLD/LFC/ALT、AFS对NAFLD/ALT的部分影响：该研究提供了令人信服的证据，证明早期AAMA、AFB和AFS是非酒精性脂肪肝的危险因素。生殖健康教育、肥胖管理和教育传播可能是预防非酒精性脂肪肝的有益策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.