Dataset Information

Higher Fibroblast Growth Factor 23 Levels Are Causally Associated With Lower Bone Mineral Density of Heel and Femoral Neck: Evidence From Two-Sample Mendelian Randomization Analysis.

ABSTRACT: Background: Previous observational studies have indicated that high levels of fibroblast growth factor 23 (FGF23), a phosphoric hormone that inhibits calcitriol synthesis, in the blood is associated with the reduced bone mineral density (BMD); however, whether this association is causal remains unclear. In this study, we conducted a Mendelian Random (MR) study to investigate whether the genetic predisposition of higher FGF23 levels was causally associated with lower BMD in adults. Methods: A two-sample MR was performed with five single nucleotide polymorphisms significantly associated with FGF23, selected as instrumental variables. Two-sample MR estimates were derived from summary-level data of large-sample genome-wide association studies for BMD and the levels of bone metabolism characteristics. Results: The two-sample MR analysis showed that for every 1-unit increase in the log-transformed blood FGF23 level (pg/mL), the decreased levels of adult heel BMD (? = -0.201, se = 0.084, P = 0.016) and femoral neck BMD (? = -0.286, se = 0.126, P = 0.022) were noted, indicative of a causal relationship based on the inverse variance weighting method. However, FGF23 levels were not correlated with adult lumbar spine BMD (? = -0.166, se = 0.193, P = 0.389), and forearm BMD (? = -0.186, se = 0.366, P = 0.610). Moreover, the two-sample MR analysis suggested that there was no evidence for associations between FGF23 and adult calcium, phosphorus, 25(OH)D, creatinine, and magnesium levels. Conclusions: This study suggests that there may be a causal relationship between blood FGF23 levels and BMD of the heel and femoral neck in adults; however, more investigations are necessary to determine whether FGF23 may be a potential biomarker and/or therapeutic target for diseases that affect bone mineralization.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7492544 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Higher Fibroblast Growth Factor 23 Levels Are Causally Associated With Lower Bone Mineral Density of Heel and Femoral Neck: Evidence From Two-Sample Mendelian Randomization Analysis.

Wang Yue Y Wang Hui H Chen Peizhan P

Frontiers in public health 20200902

<b>Background:</b> Previous observational studies have indicated that high levels of fibroblast growth factor 23 (FGF23), a phosphoric hormone that inhibits calcitriol synthesis, in the blood is associated with the reduced bone mineral density (BMD); however, whether this association is causal remains unclear. In this study, we conducted a Mendelian Random (MR) study to investigate whether the genetic predisposition of higher FGF23 levels was causally associated with lower BMD in adults. <b>Meth ...[more]

PMID: 32984251

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Project description:BackgroundOsteoporosis, which is a bone disease, is characterized by low bone mineral density and an increased risk of fractures. The heel bone mineral density is often used as a representative measure of overall bone mineral density. Lipid metabolism, which includes processes such as fatty acid metabolism, glycerol metabolism, inositol metabolism, bile acid metabolism, carnitine metabolism, ketone body metabolism, sterol and steroid metabolism, etc., may have an impact on changes in bone mineral density. While some studies have reported correlations between lipid metabolism and heel bone mineral density, the overall causal relationship between metabolites and heel bone mineral density remains unclear.Objectiveto investigate the causal relationship between lipid metabolites and heel bone mineral density using two-sample Mendelian randomization analysis.MethodsSummary-level data from large-scale genome-wide association studies were extracted to identify genetic variants linked to lipid metabolite levels. These genetic variants were subsequently employed as instrumental variables in Mendelian randomization analysis to estimate the causal effects of each lipid metabolite on heel bone mineral density. Furthermore, metabolites that could potentially be influenced by causal relationships with bone mineral density were extracted from the KEGG and WikiPathways databases. The causal associations between these downstream metabolites and heel bone mineral density were then examined. Lastly, a sensitivity analysis was conducted to evaluate the robustness of the results and address potential sources of bias.ResultsA total of 130 lipid metabolites were analyzed, and it was found that acetylcarnitine, propionylcarnitine, hexadecanedioate, tetradecanedioate, myo-inositol, 1-arachidonoylglycerophosphorine, 1-linoleoylglycerophoethanolamine, and epiandrosterone sulfate had a causal relationship with heel bone mineral density (p < 0.05). Furthermore, our findings also indicate an absence of causal association between the downstream metabolites associated with the aforementioned metabolites identified in the KEGG and WikiPathways databases and heel bone mineral density.ConclusionThis work supports the hypothesis that lipid metabolites have an impact on bone health through demonstrating a causal relationship between specific lipid metabolites and heel bone mineral density. This study has significant implications for the development of new strategies to osteoporosis prevention and treatment.

Project description:BackgroundParkinson's disease (PD) is a common degenerative nervous system disease. At present, there are certain limitations in various treatment options aimed at preventing or delaying the progression of PD. Therefore, the exploration of new drugs for PD is beneficial. Mendelian randomization (MR) analysis can be used to explore the association between drugs and diseases. In this study, MR analysis was adopted to investigate the causal relationship between 23 drugs and PD. These drugs have been approved for the treatment of different diseases, such as salicylic acid and derivatives (collectively called salicylates, e.g., aspirin, used for fever and pain relief), antithrombotic agents (e.g., warfarin, aspirin, used for preventing thrombotic events).MethodsThe GWAS data for the 23 drugs were obtained from the UK Biobank (UKB) project, while the GWAS data for PD were sourced from FinnGen. Single-Nucleotide Polymorphisms (SNPs) were selected as instrumental variables (IVs). We first performed a series of quality control steps (including MR-PRESSO) to select the appropriate SNPs. Two-sample MR analysis was performed using five different methods, including inverse variance weighting (IVW) with random-effects model, weighted median, MR-Egger, simple model, and weighted model. At the same time, sensitivity analysis was carried out using the MR-Egger and Cochran's Q test to ensure the authenticity and reliability of the results.ResultsIn MR-PRESSO, salicylates and antithrombotic agents showed statistically significant associations with PD, respectively. In the main MR analysis (IVW), there was a negative causal relationship between salicylates and PD (OR = 0.73, 95% CI = 0.54-0.98, p = .039). Similarly, there was a negative causal relationship between antithrombotic agents and PD (OR = 0.70, 95%CI = 0.52-0.96, p = .027). No statistically significant association was found between the remaining 21 drugs and PD.ConclusionThis MR study demonstrated that salicylates and antithrombotic agents can reduce the risk of PD, thus providing a novel avenue for future drug exploration in PD.

Dataset Information

Higher Fibroblast Growth Factor 23 Levels Are Causally Associated With Lower Bone Mineral Density of Heel and Femoral Neck: Evidence From Two-Sample Mendelian Randomization Analysis.

Publications

Higher Fibroblast Growth Factor 23 Levels Are Causally Associated With Lower Bone Mineral Density of Heel and Femoral Neck: Evidence From Two-Sample Mendelian Randomization Analysis.

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