The Causal Effect of Urate Level on Female Infertility: A Mendelian Randomization Study.

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Metabolites Pub Date : 2024-09-25 DOI:10.3390/metabo14100516

Jiawei Sun, Ting Shen, Yining Guan, Yixin Jiang, Xiaoling Xu

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Abstract

Background/objective: This study aimed to investigate the causal relationship between urate level and female infertility using Mendelian randomization (MR) analysis.

Methods: To identify instrumental variables, we selected independent genetic loci associated with serum urate levels in individuals of European ancestry, utilizing data from large-scale genome-wide association studies (GWAS). The GWAS dataset included information on serum urate levels from 288,649 CKDGen participants. Female infertility data, including different etiologic classifications, consisted of 13,142 female infertility patients and 107,564 controls. We employed four MR methods, namely inverse variance weighted (IVW), MR-Egger, weighted median, and weighted model, to investigate the causal relationship between urate levels and female infertility. The Cochran Q-test was used to assess heterogeneity among single nucleotide polymorphisms (SNPs), and the MR-Egger intercept test was employed to evaluate the presence of horizontal pleiotropy. Additionally, a "leave-one-out" sensitivity analysis was conducted to examine the influence of individual SNPs on the MR study.

Results: The IVW analysis demonstrated that elevated serum urate levels increased the risk of female infertility (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07-1.33). Furthermore, serum urate levels were found to be associated with infertility due to cervical, vaginal, or other unknown causes (OR = 1.16, 95% CI: 1.06-1.26), also confirmed by other methods. Heterogeneity among instrumental variables was assessed using Cochran's Q-test (p < 0.05), so a random-effects IVW approach was employed in the effects model. The MR-Egger intercept test indicated no presence of horizontal pleiotropy. A "leave-one-out" sensitivity analysis was conducted, demonstrating that no individual SNP had a substantial impact on the overall findings.

Conclusions: In the European population, the urate level is significantly and causally associated with an increased risk of female infertility.

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尿酸水平对女性不孕的因果效应：孟德尔随机研究

背景/目的本研究旨在利用孟德尔随机分析法（MR）研究尿酸水平与女性不孕症之间的因果关系：为了确定工具变量，我们利用大规模全基因组关联研究（GWAS）的数据，选择了与欧洲血统个体血清尿酸水平相关的独立遗传位点。GWAS 数据集包括 288,649 名 CKDGen 参与者的血清尿酸水平信息。女性不孕症数据（包括不同的病因分类）包括 13,142 名女性不孕症患者和 107,564 名对照者。我们采用了反方差加权（IVW）、MR-Egger、加权中位数和加权模型四种 MR 方法来研究尿酸水平与女性不孕症之间的因果关系。Cochran Q 检验用于评估单核苷酸多态性（SNPs）之间的异质性，MR-Egger 截距检验用于评估是否存在水平多效性。此外，还进行了 "leave-one-out "敏感性分析，以检查单个 SNP 对 MR 研究的影响：IVW分析表明，血清尿酸水平升高会增加女性不孕症的风险（比值比 [OR] = 1.18，95% 置信区间 [CI]：1.07-1.33）。此外，血清尿酸水平还与宫颈、阴道或其他不明原因导致的不孕有关（OR = 1.16，95% CI：1.06-1.26），其他方法也证实了这一点。使用 Cochran's Q 检验评估了工具变量之间的异质性（P < 0.05），因此在效应模型中采用了随机效应 IVW 方法。MR-Egger截距检验表明不存在水平多效性。进行了 "撇一除一 "敏感性分析，结果表明没有单个 SNP 对总体结果产生实质性影响：结论：在欧洲人群中，尿酸水平与女性不孕症风险的增加有显著的因果关系。

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

Metabolites Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

5.70

自引率

7.30%

发文量

1070

审稿时长

17.17 days

期刊介绍： Metabolites (ISSN 2218-1989) is an international, peer-reviewed open access journal of metabolism and metabolomics. Metabolites publishes original research articles and review articles in all molecular aspects of metabolism relevant to the fields of metabolomics, metabolic biochemistry, computational and systems biology, biotechnology and medicine, with a particular focus on the biological roles of metabolites and small molecule biomarkers. Metabolites encourages scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on article length. Sufficient experimental details must be provided to enable the results to be accurately reproduced. Electronic material representing additional figures, materials and methods explanation, or supporting results and evidence can be submitted with the main manuscript as supplementary material.