The study investigated the causal relationships between spermidine levels and CVD risk factors using a bi-directional MR approach. Employing genetic variants from extensive GWAS datasets as IVs, the study aimed to determine whether spermidine levels can influence CVD risk factors such as blood pressure, blood glucose, and lipid profiles, and vice versa. The findings suggest a protective role of elevated spermidine levels against hypertension, elevated blood glucose, and lipid profiles (LDL-C and HDL-C). Specifically, increased spermidine levels were significantly associated with lower risk of hypertension (IVW beta = -0.0013453913, p = 0.01597648) and suppression risk of elevated blood glucose (IVW beta = -0.08061330, p = 0.02450205). Additionally, there was a notable association with lipid modulation, showing a decrease in LDL-C (IVW beta = -0.01849161, p = 0.01086728) and an increase in HDL-C (IVW beta = 0.0044608332, P = 0.01760051). Conversely, the influence of CVD risk factors on spermidine levels was minimal, with the exception that elevated blood glucose levels resulted in reduced spermidine levels. (IVW beta = -0.06714391, P = 0.01096123). These results underline the potential of spermidine as a modifiable dietary target for the prevention and management of cardiovascular diseases. Further investigations are warranted to explore the underlying biological mechanisms and the applicability of these findings in broader and diverse populations.

OBJECTIVE: This study aimed to investigate the heritability of various obesity indices and their shared genetic factors with cardiometabolic traits in the Chinese nuclear family.
METHODS: A total of 1270 individuals from 538 nuclear families were included in this cross-sectional study. Different indices were used to quantify fat mass and distribution, including body index mass (BMI), visceral fat index (VFI), and body fat percent (BFP). Heritability and genetic correlations for all quantitative traits were estimated using variance component models. The susceptibility-threshold model was utilized to estimate the heritability for binary traits.
RESULTS: Heritability estimates for obesity indices were highest for BMI (59%), followed by BFP (49%), and VFI (40%). Heritability estimates for continuous cardiometabolic traits varied from 24% to 50%. All obesity measures exhibited consistently significant positive genetic correlations with blood pressure, fasting blood glucose, and uric acid (rG range: 0.26-0.57). However, diverse genetic correlations between various obesity indices and lipid profiles were observed. Significant genetic correlations were limited to specific pairs: BFP and total cholesterol (rG = 0.24), BFP and low-density lipoprotein cholesterol (rG = 0.25), and VFI and triglyceride (rG = 0.33).
CONCLUSIONS: The genetic overlap between various obesity indices and cardiometabolic traits underscores the importance of pleiotropic genes. Further studies are warranted to investigate specific shared genetic and environmental factors between obesity and cardiometabolic diseases.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder. Recent studies indicate that GERD may exert systemic effects, potentially elevating the risk of severe infections, including sepsis. Nevertheless, the causal relationship between GERD and sepsis, as well as sepsis-related 28-day mortality, remains uncertain.
OBJECTIVE: The aim of this study is to investigate the causal relationship between GERD and the risk of sepsis, including 28-day mortality of sepsis.
METHODS: This study utilized a two-sample Mendelian Randomization (MR) approach to analyze data from publicly available genome-wide association studies (GWAS) databases ( https://gwas.mrcieu.ac.uk/ ). The analysis comprised 129,080 cases and 473,524 controls for GERD; 11,643 patients and 474,841 controls for sepsis; and 1,896 patients and 484,588 controls for 28-day mortality from sepsis. The objective was to evaluate the causal impact of GERD on the risk of sepsis and 28-day sepsis mortality. Genetic variation data pertinent to GERD were obtained from the most recent genome-wide association studies (GWAS). The primary analysis employed the Inverse Variance Weighted (IVW) method. Sensitivity and pleiotropy analyses were performed to validate the robustness of the findings.
RESULTS: MR analysis revealed a notable link between genetically predicted GERD and increased sepsis risk (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.24-1.52; p = 2.79 × 10-9). Moreover, GERD correlated with elevated 28-day mortality of sepsis (OR 1.44, 95% CI 1.11-1.85; p = 5.34 × 10-3). These results remained consistent throughout various sensitivity analyses, indicating their resilience against potential pleiotropy and other biases.
CONCLUSIONS: This study indicates that genetic predisposition to GERD may be linked to an elevated risk of sepsis and its associated 28-day mortality. However, the study does not establish a direct causal relationship for GERD itself, nor does it assess the impact of GERD treatment. Further research is needed to explore the underlying mechanisms and potential therapeutic interventions involved.

UNASSIGNED: Previous studies have shown a connection between physical activity and migraines, but they don\'t prove a cause-and-effect relationship due to potential biases in observational methods.
UNASSIGNED: Utilizing accelerometer-measured physical activity data from a cohort of 377,234 participants in the UK Biobank and information from 599,356 European migraine patients (including 48,975 cases and 550,381 controls) obtained from 24 cohorts, we performed a bidirectional Mendelian randomization analysis to investigate the genetic bidirectional causal relationship between accelerometer-measured physical activity and migraines.
UNASSIGNED: Research findings indicated a slight negative genetic correlation between \"average acceleration\" physical activity (rg  = -0.091, p = 0.011), overall physical activity (rg  = -0.081, p = 0.017), and migraine. Nevertheless, no shared genetic components were observed between migraine and \"fraction of accelerations > 425 mg\" of physical activity (rg  = -0.124, p = 0.076). The study results also demonstrated a lack of genetic bidirectional causality between accelerometer-measured physical activity and migraine (\"average acceleration\", OR = 1.002, 95% CI 0.975-1.031, p = 0.855, \"fraction of accelerations > 425 mg\", OR = 1.127, 95% CI 0.802-1.583, p = 0.488, overall physical activity, OR = 0.961, 95% CI 0.713-1.296, p = 0.799), and vice versa. Additionally, this lack of causal association persists even after adjusting for obesity (OR = 1.005, p = 0.578), education (OR = 1.019, p = 0.143), and depression (OR = 1.005, p = 0.847), either separately or simultaneously.
UNASSIGNED: The Mendelian randomization results based on genetic data do not provide support for a causal association between physical activity and migraine.

BACKGROUND: Urolithiasis is a highly prevalent global disease closely associated with metabolic factors; however, the causal relationship between blood metabolites and urolithiasis remains poorly understood.
METHODS: In our study, we employed a bi-directional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between urolithiasis and metabolites. The random-effects inverse-variance weighted (IVW) estimation method was utilized as the primary approach, complemented by several other estimators including MR-Egger, weighted median, colocalization and MR-PRESSO. Furthermore, the study included replication and meta-analysis. Finally, we conducted metabolic pathway analysis to elucidate potential metabolic pathways.
RESULTS: After conducting multiple tests for correction, glycerol might contribute to the urolithiasis and dehydroisoandrosterone sulfate (DHEA-S) might inhibit this process. Furthermore, several blood metabolites had shown potential associations with a causal relationship. Among the protective metabolites were lipids (dehydroisoandrosterone sulfate and 1-stearoylglycerol (1-monostearin)), amino acids (isobutyrylcarnitine and 2-aminobutyrate), a keto acid (acetoacetate) and a carbohydrate (mannose). The risk metabolites included lipids (1-palmitoylglycerophosphoethanolamine, glycerol and cortisone), a carbohydrate (erythronate), a peptide (pro-hydroxy-pro) and a fatty acid (eicosenoate). In reverse MR analysis, urolithiasis demonstrated a statistically significant causal relationship with butyrylcarnitine, 3-methyl-2-oxobutyrate, scyllo-inositol, leucylleucine and leucylalanine. However, it was worth noting that none of the blood metabolites exhibited statistical significance after multiple corrections. Additionally, we identified one metabolic pathway associated with urolithiasis.
CONCLUSIONS: The results we obtained demonstrate the causal relevance between two metabolites and urolithiasis, as well as identify one metabolic pathway potentially associated with its development. Given the high prevalence of urolithiasis, further investigations are encouraged to elucidate the mechanisms of these metabolites and explore novel therapeutic strategies.

Observational studies have suggested the potential benefits of several medications for Parkinson\'s disease (PD) and their potential for repurposing. However, the conclusions drawn from these studies are not entirely consistent. To address this inconsistency, we used the two-sample Mendelian randomization (MR) method to explore the putative causal relationships between 23 medications and the risk and progression of PD. We applied inverse-variance weighted meta-analysis (IVW) to combine MR estimates. Additionally, sensitivity analyses were conducted to evaluate the robustness of the results. Our genetic evidence suggests that thyroid preparations and calcium channel blockers reduce the risk of PD, and salicylic acid and derivatives slow the progression of PD motor symptoms. Additionally, genetic evidence also suggests that four medications were associated with PD risk or progression, but the sensitivity analysis revealed that three of the medications may have interference caused by reverse causality. Our findings suggest that there are weak causal relationships between several medications and the risk or progression of PD. Though further replication studies are needed to verify these findings, these new insights may help in understanding the etiology of the disease, generate new clues related to drug discovery, and quantify the risk of future drug intake.

UNASSIGNED: Benign prostatic hyperplasia (BPH) is a common disease occurring in elderly and middle-aged men, and cardiovascular diseases (CVDs) are one of the major causes of death worldwide. Many observational studies examined have found a strong association between BPH and CVDs, but the causal relationship between them is unclear. The aim of this study was to determine the causal relationship between BPH and CVDs, specifically five diseases: stroke, coronary heart disease (CHD), heart failure, myocardial infarction (MI), and atrial fibrillation (AF).
UNASSIGNED: In this study, we obtained single nucleotide polymorphisms (SNPs) of patients with BPH from the UK Biobank database and patients with CVDs from the UK Biobank, the HERMES Consortium, and the FinnGen Genome Database, each used as a genetic tool for a Mendelian randomization (MR) study. We used conventional MR analysis to assess potential causal direction between BPH and CVDs, as well as MR-Egger, MR-PRESSO, model-based estimation (MBE) and weighted median methods for sensitivity analysis.
UNASSIGNED: Using a bidirectional two-sample MR study, we found that BPH patients had an increased risk of developing CHD (ConMix OR = 1.152, 95% CI: 1.011-1.235, p = 0.035) and MI (ConMix OR = 1.107.95% CI: 1.022-1.164, p = 0.013), but a decreased risk of stroke (ConMix OR = 0.872, 95% CI: 0.797-0.926, p = 0.002). The reverse study was not statistically significant and further research may be needed.
UNASSIGNED: Our study suggests a potential causal relationship between BPH and CVDs. BPH appears to be a risk factor for CHD and MI, but it may be protective against stroke. There was no evidence of a causal association in the reverse study, and a larger sample size was needed in follow-up to further explore the potential association.

暂无摘要。

暂无摘要。

UNASSIGNED: Preeclampsia/eclampsia (PE), a critical complication during pregnancy, has been suggested to correlate with immune cell phenotypes and levels of circulating inflammatory proteins. Our study aimed to employ a two-sample mendelian randomization (MR) analysis to assess the potential causal effects of immune cell phenotypes and circulating inflammatory proteins on the onset of PE.
UNASSIGNED: We utilized summary-level data from genome-wide association studies (GWAS). This included statistics for 371 immune cell phenotypes from 3,757 individuals in the Sardinian founder population, and data on 91 circulating inflammatory proteins from 14,824 European ancestry participants. Additionally, genetic associations related to PE were extracted from the FinnGen consortium, involving 1,413 cases and 287,137 controls. We applied inverse variance weighting (IVW) and supplementary methods like MR-Egger, weighted median, and weighted mode to comprehensively assess potential causal links.
UNASSIGNED: Our analysis revealed significant causal associations of several immune cells type and inflammatory proteins with PE. Out of the immune cell phenotypes analyzed, six immune phenotypes emerged as significant risk factors (p <0.01), mainly include CD4 on activated and secreting CD4 regulatory T cells, CD28 on CD39+ CD4+ T cells, CD127- CD8+ T cell absolute cell (AC) counts, HLA DR on HLA DR+ CD8+ T cell, CD66b on CD66b++ myeloid cells, and HLA DR on dendritic cells. And ten were identified as protective factors (p <0.01). Such as CD45 on CD33br HLA DR+ CD14-, CD33+ HLA DR+ AC, CD33+ HLA DR+ CD14- AC, CD33+ HLA DR+ CD14dim AC, CD27 on CD24+ CD27+ B cell, CD20- CD38- %B cell, IgD- CD24- %B cell CD80 on plasmacytoid DC, CD25 on CD4+ T cell, and CD25 on activated & secreting CD4 regulatory T cell. Furthermore, among the inflammatory proteins studied, five showed a significant association with PE, with three offering protective effects mainly include that C-X-C motif chemokine 1, tumor necrosis factor ligand superfamily member 14, and C-C motif chemokine 19 and two exacerbating PE risk such as STAM-binding domain and Interleukin-6 (p <0.05).
UNASSIGNED: Our study highlights the pivotal roles played by diverse immune cell phenotypes and circulating inflammatory proteins in the pathophysiology of PE. These findings illuminate the underlying genetic mechanisms, emphasizing the criticality of immune regulation during pregnancy. Such insights could pave the way for novel intervention strategies in managing PE, potentially enhancing maternal and neonatal health outcomes.