The effect of systemic iron status on osteoarthritis: A mendelian randomization study

Ruan, Guangfeng; Lu, Shi‐Long; Zhu, Zhaohua; Chen, Shibo; Zeng, Muhui; Lu, Ming; Xue, Song; Zhu, Jianwei; Cao, Peihua; Chen, Tianyu; Wang, Xiaoshuai; Li, Shengfa; Li, Jia; Liu, Yu; Liu, Yanqi; Zhang, Yan; Ding, Changhai

doi:10.3389/fgene.2023.1122955

Cited by 7 publications

(4 citation statements)

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“… 25 This dataset has a large sample size and has been widely used in MR analyses related to KOA, with acceptable imputation quality. 26 …”

Section: Methodsmentioning

confidence: 99%

“…25 This dataset has a large sample size and has been widely used in MR analyses related to KOA, with acceptable imputation quality. 26 Figure 1 The design of bidirectional Mendelian randomization (MR) study. The "×" means that genetic variants are not associated with confounders or cannot be directly involved in outcome but via the exposure pathway.…”

Section: Sources Of Datamentioning

confidence: 99%

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A Bidirectional Mendelian Randomization Study of Sarcopenia-Related Traits and Knee Osteoarthritis

Zhang,

Zhang

et al. 2023

CIA

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Background: With the development of population aging worldwide, sarcopenia and knee osteoarthritis (KOA), two age-related diseases, will continue to impose increasing medical and economic burdens on the society. Previous studies have discovered an association between the two, but the causality remains controversial, and it is difficult to eliminate confounding factors. Therefore, a Mendelian randomization (MR) study was conducted to overcome these confounding factors and investigate the causal relationship between sarcopenia and KOA. Objective: The present work focused on assessing the causality between KOA and sarcopenia, so as to provide new strategies to prevent and treat these two conditions in clinic. Methods: We registered the title with PROSPERO (ID: CRD42023421096). The two-sample bidirectional MR analysis was conducted in two steps, with sarcopenia being the exposure whereas KOA being the outcome in the first step, and vice versa in the second step. Genomewide association studies (GWAS) data on low hand-grip strength (n=256,523), walking pace (n=459,915), appendicular lean mass (ALM, n=450,243), and KOA (n=403,124) were obtained from the UK Biobank. Methods such as the inverse variance weighted (IVW) and weighted median were utilized for assessing the causality of KOA with sarcopenia, and sensitivity analyses were also conducted. Results: In the main MR analysis using the IVW method, evidence suggested that low hand-grip strength, walking pace, and ALM had adverse effects on KOA (p-value 0.0001, odds ratio (OR) 1.4569, 95% confidence interval (CI) 1.2007-1.7677 for low hand-grip strength; p-value 0.0003, OR 1.1500, 95% CI 1.050-1.183 for ALM; p-value 5.29E-19, OR 0.0932, 95% CI 0.0553-0.1572 for walking pace). However, there was no causality of KOA with sarcopenia in the opposite direction. Conclusion: Our study suggests an obvious unidirectional causality of KOA with sarcopenia, and supports the notion that patients with sarcopenia are more susceptible to the development of KOA.

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“… 25 This dataset has a large sample size and has been widely used in MR analyses related to KOA, with acceptable imputation quality. 26 …”

Section: Methodsmentioning

confidence: 99%

Section: Sources Of Datamentioning

confidence: 99%

A Bidirectional Mendelian Randomization Study of Sarcopenia-Related Traits and Knee Osteoarthritis

Zhang,

Zhang

et al. 2023

CIA

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“…Previous studies have found rare mutations in certain genes that can lead to hereditary OA, even results in severe OA ( 35 – 37 ). At least 100 risk loci associated with OA have also been identified by genome wide-association studies ( 38 , 39 ).…”

Section: Discussionmentioning

confidence: 99%

Consensus cluster analysis of apoptosis-related genes in patients with osteoarthritis and their correlation with immune cell infiltration

Yu,

Zhang,

et al. 2023

Front. Immunol.

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BackgroundOsteoarthritis (OA) progression involves multiple factors, including cartilage erosion as the basic pathological mechanism of degeneration, and is closely related to chondrocyte apoptosis. To analyze the correlation between apoptosis and OA development, we selected apoptosis genes from the differentially expressed genes (DEGs) between OA and normal samples from the Gene Expression Omnibus (GEO) database, used lasso regression analysis to identify characteristic genes, and performed consensus cluster analysis to further explore the pathogenesis of this disease.MethodsThe Gene expression profile datasets of OA samples, GSE12021 and GSE55235, were downloaded from GEO. The datasets were combined and analyzed for DEGs. Apoptosis-related genes (ARGs) were collected from the GeneCards database and intersected with DEGs for apoptosis-related DEGs (ARDEGs). Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to obtain characteristic genes, and a nomogram was constructed based on these genes. A consensus cluster analysis was performed to divide the patients into clusters. The immune characteristics, functional enrichment, and immune infiltration statuses of the clusters were compared. In addition, a protein–protein interaction network of mRNA drugs, mRNA-transcription factors (TFs), and mRNA-miRNAs was constructed.ResultsA total of 95 DEGs were identified, of which 47 were upregulated and 48 were downregulated, and 31 hub genes were selected as ARDEGs. LASSO regression analysis revealed nine characteristic genes: growth differentiation factor 15 (GDF15), NAMPT, TLR7, CXCL2, KLF2, REV3L, KLF9, THBD, and MTHFD2. Clusters A and B were identified, and neutrophil activation and neutrophil activation involved in the immune response were highly enriched in Cluster B, whereas protein repair and purine salvage signal pathways were enriched in Cluster A. The number of activated natural killer cells in Cluster B was significantly higher than that in Cluster A. GDF15 and KLF9 interacted with 193 and 32 TFs, respectively, and CXCL2 and REV3L interacted with 48 and 82 miRNAs, respectively.ConclusionARGs could predict the occurrence of OA and may be related to different degrees of OA progression.

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“…Many recent studies have used MR methods to explore risk or protective factors for KOA [32][33][34]. However, few studies have examined the association between diet and KOA using MR.…”

Section: Plos Onementioning

confidence: 99%

Causal relationship between diet and knee osteoarthritis: A Mendelian randomization analysis

Lv,

Liang,

Liu

et al. 2024

PLoS ONE

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Background Knee osteoarthritis (KOA) is a common disabling joint disease that affects millions of people worldwide. Diet may play a role in the etiology and progression of KOA, but evidence for a causal relationship is limited. We aimed to investigate the causal impact of dietary intake on KOA risk using Mendelian randomization (MR). Methods We used summary-level data from genome-wide association studies (GWAS) including dietary intake (n = 335, 394–462, 342), and KOA (n = 403, 124). We selected 6–77 genetic variants as instrumental variables for 18 dietary factors, including processed meat, poultry, beef, oily fish, non-oily fish, pork, lamb, frequency of alcohol intake, alcoholic beverages, tea, coffee, dried fruit, cereals, cheese, bread, cooked vegetables, salad/raw vegetables, and fresh fruit. We performed univariate and multivariate MR analyses to estimate the causal effect of each dietary factor on KOA risk. We also performed some sensitivity analyses to assess the validity of the MR hypothesis. Results We found that higher coffee intake was associated with increased KOA risk, whereas higher intake of dried fruits, grains, cheese, and oily fish was associated with reduced KOA risk. After multivariate adjustment, we found that coffee and oily fish intake may affect KOA through obesity, body mass index (BMI), diabetes, hypertension, and prolonged standing. Sensitivity analyses did not reveal any evidence of pleiotropy. Conclusions Our study provides new causal evidence that dietary intake may influence KOA risk. Specifically, we suggest that increased intake of dried fruits, grains, cheese, and oily fish and decreased coffee intake may be beneficial in preventing and mitigating KOA. further studies are needed to elucidate the underlying mechanisms and to confirm our findings in different populations.

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The effect of systemic iron status on osteoarthritis: A mendelian randomization study

Cited by 7 publications

References 50 publications

A Bidirectional Mendelian Randomization Study of Sarcopenia-Related Traits and Knee Osteoarthritis

A Bidirectional Mendelian Randomization Study of Sarcopenia-Related Traits and Knee Osteoarthritis

Consensus cluster analysis of apoptosis-related genes in patients with osteoarthritis and their correlation with immune cell infiltration

Causal relationship between diet and knee osteoarthritis: A Mendelian randomization analysis

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