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Abstract With the aging of the population, sarcopenia has become more common. Studies have shown a broad association between liver disease and sarcopenia. However, this link remains unclear. Our study explored the link between NAFLD and sarcopenia and predicting the pathogenesis. To begin, we investigated the causal relationship and genetic correlation between them using MR and LDSC. Second, each GWAS was annotated by MAGMA. The annotated genes were analyzed for pleiotropy using the PLACO approach. Finally, functional analysis was conducted on the identified pleiotropic genes. We observed a significant genetic correlation between NAFLD and sarcopenia. Subsequently, we conducted gene-level pleiotropy analysis using PLACO and identified a total of 153 genes with pleiotropic effects. Functional analysis revealed enrichment of these genes in various tissues, including pancreas, liver, heart, blood, brain, and muscle, with involvement in cellular regulation, intracellular function, and antigen response. Moreover, our MR analysis provided evidence of a causal relationship between NAFLD and sarcopenia. Our study has discovered the genetic and causal relationships between NAFLD and sarcopenia, providing further insights into their pathophysiological mechanisms. The identification of pleiotropic genes also offers potential targets for future drug therapies aimed at controlling or treating NAFLD and sarcopenia.

Abstract Acute respiratory distress syndrome (ARDS) is a major disease that threatens the life and health of neonates. Vitamin A (VA) can participate in early fetal lung development and affect lung immune function. Researches revealed that the serum VA level in premature infants with ARDS was lower than that in premature infants without ARDS of the same gestational age, and premature infants with VA deficiency (VAD) were more likely to develop ARDS. Moreover, the VA levels can be used as a predictor of the development and severity of neonatal ARDS. However, the critical question here is; Does ARDS develop due to VAD in these systemic diseases? Or does ARDS develop because these diseases cause VAD? We hypothesize that VAD may aggravate neonatal ARDS by affecting immunity, metabolism, barriers and other pathways. In this article, we used multiomics analysis to find that VAD may aggravate ARDS mainly through the Fc epsilon RI signaling pathway, the HIF-1 signaling pathway, glutathione metabolism, and valine, leucine and isoleucine degradation signaling pathways, which may provide the molecular pathogenic mechanism behind the pathology of VAD-aggravated ARDS and can also provide potential molecular targets for subsequent research on ARDS.

AimObservational studies have reported that levels of vitamin D were associated with the incidence of chronic obstructive pulmonary disease (COPD), but the relationship between them may have been confounded in previous studies. In this study, we aimed to determine the relationship between the levels of 25-hydroxyvitamin D (25OHD) and the risk of COPD by two-sample Mendelian randomization (MR) analysis.MethodsSummary statistics for 25OHD and COPD in this study were obtained from the EBI (n = 496,946) consortium and Finn (n = 187,754) consortium. MR was adopted to explore the effect of the genetically predicted levels of 25OHD on the risk of COPD. Based on three assumptions of MR analysis, inverse variance weighting was used as the main analysis. To make our results more robust and reliable, MR Egger’s intercept test, Cochran’s Q test, funnel plot, and “leave-one-out” sensitivity analysis were used to assess the potential pleiotropy and heterogeneity in this study. Then, colocalization analysis and MR Steiger approaches were used to estimate the possible directions of estimates between them. Finally, we analyzed the causal associations between the four core genes (DHCR7, GC, CYP2R1, and CYP24A1) of vitamin D and the levels of 25OHD or the risk of COPD.ResultsOur results showed that each 1 standard deviation (SD) increase in the genetically predicted 25OHD level was associated with a 57.2% lower relative risk of COPD [odds ratio (OR): 0.428, 95% Cl: 0.279–0.657, p = 1.041 × 10−4], and the above association was also verified by maximum likelihood (OR: 0.427, 95% Cl: 0.277–0.657, p = 1.084 × 10−4), MR–Egger (OR: 0.271, 95% CI: 0.176–0.416, p = 2.466 × 10−4), MR-PRESSO (OR: 0.428, 95% Cl: 0.281–0.652, p = 1.421 × 10−4) and MR-RAPS (OR: 0.457, 95% Cl: 0.293–0.712, p = 5.450 × 10−4). Furthermore, colocalization analyses (rs3829251, PP.H4 = 0.99) and MR Steiger (“TRUE”) also showed a reverse association between them. Besides, the core genes of vitamin D also showed similar results except for CYP24A1.ConclusionOur findings provide evidence for a reverse association between genetically predicted 25OHD levels and COPD risk. Taking measures to supplement 25OHD may help reduce the incidence of COPD.

ObjectiveInvestigating the causal relationship between rheumatoid arthritis (RA) and atlantoaxial subluxation (AAS) and identifying and quantifying the role of C-reactive protein (CRP) as a potential mediator.MethodsUsing summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of genetically predicted rheumatoid arthritis (14,361 cases, and 43,923 controls) and AAS (141 cases, 227,388 controls) was performed. Furthermore, we used two-step MR to quantitate the proportion of the effect of c-reactive protein-mediated RA on AAS.ResultsMR analysis identified higher genetically predicted rheumatoid arthritis (primary MR analysis odds ratio (OR) 0.61/SD increase, 95% confidence interval (CI) 1.36-1.90) increased risk of AAS. There was no strong evidence that genetically predicted AAS had an effect on rheumatoid arthritis risk (OR 1.001, 95% CI 0.97-1.03). The proportion of genetically predicted rheumatoid arthritis mediated by C-reactive protein was 3.7% (95%CI 0.1%−7.3%).ConclusionIn conclusion, our study identified a causal relationship between RA and AAS, with a small proportion of the effect mediated by CRP, but a majority of the effect of RA on AAS remains unclear. Further research is needed on additional risk factors as potential mediators. In clinical practice, lesions of the upper cervical spine in RA patients need to be given more attention.

Galacto-oligosaccharides (GOS) are oligosaccharides formed by β-galactosidase transgalactosylation. GOS is an indigestible food component that can pass through the upper gastrointestinal tract relatively intact and ferment in the colon to produce short-chain fatty acids (SCFAs) that further regulate the body’s intestinal flora. GOS and other prebiotics are increasingly recognized as useful food tools for regulating the balance of colonic microbiota-human health. GOS performed well compared to other oligosaccharides in regulating gut microbiota, body immunity, and food function. This review summarizes the sources, classification, preparation methods, and biological activities of GOS, focusing on the introduction and summary of the effects of GOS on ulcerative colitis (UC), to gain a comprehensive understanding of the application of GOS.

Objectives: Although it has long been reported that high levels of cystatin C could contribute to the development of osteoporosis in some studies, no evidence has established a causal association between them thus far.Methods: A Mendelian randomization (MR) study was conducted to determine the causal effect of cystatin C on osteoporosis based on public databases obtained from separately published genome-wide association studies (GWASs). The single-nucleotide polymorphisms (SNPs) for cystatin C were extracted from the MR-Base (CKDGen, 33,152 participants), and the SNPs for osteoporosis were extracted from the United Kingdom Biobank project (United Kingdom Biobank, including 5,266 osteoporosis cases and 331,893 controls). We defined the odds ratio (OR) of IVW methods as the primary outcome. In addition, weighted median and MR–Egger regressions were used in the sensitivity analysis.Results: In IVW, we found that genetically predicted cystatin C was causally associated with the risk of osteoporosis with an OR of 1.02 [95% confidence interval (CI) = 1.003–1.025, p = 0.01]. In the further sensitivity analysis, weighted median regression also showed directionally similar estimates (OR = 1.02, 95% CI = 1.005–1.03, p = 0.005), and MR–Egger regression (OR = 1.02, 95% CI = 1.000–1.036, p = 0.15) revealed similar estimates but with lower precision. The funnel plot, MR–Egger intercept, and MR-PRESSO all indicate that no directional pleiotropic effect was observed.Conclusion: In conclusion, our MR study showed evidence of a causal association between serum cystatin C levels and osteoporosis, which also needs to be verified by studies with larger sample sizes in the future. Early monitoring of cystatin C may enable us to prevent osteoporosis-related diseases.