Genetic Causal Association between Iron Status and Osteoarthritis: A Two-Sample Mendelian Randomization.
Genetic Causal Association between Iron Status and Osteoarthritis: A Two-Sample Mendelian Randomization.
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DOI：
10.3390/nu14183683
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发表时间：
2022-09-06
期刊：
影响因子：
5.9
通讯作者：
Shen B
中科院分区：
文献类型：
--
作者：
Xu J;Zhang S;Tian Y;Si H;Zeng Y;Wu Y;Liu Y;Li M;Sun K;Wu L;Shen B
目的：观察性研究表明铁状态与骨关节炎（OA）之间存在关联。然而，由于时序性难以确定，它们之间的因果关系仍然难以捉摸。本研究基于大规模人群的全基因组关联研究（GWASs）汇总数据，探讨了铁状态与OA之间的遗传因果关系。方法：首先，我们采取了一系列质量控制步骤来选择与暴露密切相关的符合条件的仪器snp。采用双样本孟德尔随机化（MR）分析了铁状态与OA之间的遗传因果关系。采用反方差加权法（IVW）、MR-Egger法、加权中位数法、简单模式法和加权模式法进行分析。结果主要基于随机效应（IVW），其次是敏感性分析。采用IVW和MR-Egger进行异质性检验。MR-Egger也被用于多效性测试。使用Leave-one-SNP-out分析来鉴定具有潜在影响的单核苷酸多态性（snp）。采用最大似然、惩罚加权中位数和IVW（固定效应）进一步验证结果的可靠性。结果：IVW结果显示，转铁蛋白饱和度与膝关节骨关节炎（KOA）、髋关节骨关节炎（HOA）、KOA或HOA呈正相关（p < 0.05, or < 0.01），与HOA、KOA或HOA呈负相关（p < 0.05, or < 1）。异质性检验结果显示，我们的IVW分析结果基本不存在异质性（p < 0.05）。多效性试验结果显示，我们的IVW分析不存在多效性（p < 0.05）。最大似然、惩罚加权中位数和IVW（固定效应）的分析结果与我们的IVW结果一致。血清铁和铁蛋白与OA之间未发现遗传因果关系。结论：本研究提供了铁状态与OA之间因果关系的证据，为OA的遗传研究提供了新的见解。
Objective: Observational studies have shown the association between iron status and osteoarthritis (OA). However, due to difficulties of determining sequential temporality, their causal association is still elusive. Based on the summary data of genome-wide association studies (GWASs) of a large-scale population, this study explored the genetic causal association between iron status and OA. Methods: First, we took a series of quality control steps to select eligible instrumental SNPs which were strongly associated with exposure. The genetic causal association between iron status and OA was analyzed using the two-sample Mendelian randomization (MR). Inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods were used for analysis. The results were mainly based on IVW (random effects), followed by sensitivity analysis. IVW and MR-Egger were used for heterogeneity testing. MR-Egger was also used for pleiotropy testing. Leave-one-SNP-out analysis was used to identify single nucleotide polymorphisms (SNPs) with potential impact. Maximum likelihood, penalized weighted median, and IVW (fixed effects) were performed to further validate the reliability of results. Results: IVW results showed that transferrin saturation had a positive causal association with knee osteoarthritis (KOA), hip osteoarthritis (HOA) and KOA or HOA (p < 0.05, OR > 1), and there was a negative causal association between transferrin and HOA and KOA or HOA (p < 0.05, OR < 1). The results of heterogeneity test showed that our IVW analysis results were basically free of heterogeneity (p > 0.05). The results of the pleiotropy test showed that there was no pleiotropy in our IVW analysis (p > 0.05). The analysis results of maximum likelihood, penalized weighted median and IVW (fixed effects) were consistent with our IVW results. No genetic causal association was found between serum iron and ferritin and OA. Conclusions: This study provides evidence of the causal association between iron status and OA, which provides novel insights to the genetic research of OA.
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影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
5.3
作者：
Jing X;Du T;Li T;Yang X;Wang G;Liu X;Jiang Z;Cui X
通讯作者：
Cui X
DOI：
10.1080/17474124.2021.1949290
发表时间：
2021-07-21
影响因子：
3.9
作者：
Chen, Jie;Chen, Xuejie;Hesketh, Therese
通讯作者：
Hesketh, Therese
影响因子：
7
作者：
de Boer, T. N.;van Spil, W. E.;Mastbergen, S. C.
通讯作者：
Mastbergen, S. C.
影响因子：
13.3
作者：
Lopez de Figueroa, Paloma;Lotz, Martin K.;Blanco, Francisco J.;Carames, Beatriz
通讯作者：
Carames, Beatriz