Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 19, 2023

Inflammation plays a role in the pathogenesis of acute-on-chronic liver failure (ACLF), however, whether there is causal relationship between inflammation and ACLF remains unclear. A two-sample Mendelian randomization (MR) approach was used to investigate systemic inflammatory regulators ACLF. The study analyzed 41 cytokines growth factors from 8,293 individuals extracted genome-wide association (GWAS) meta-analysis database involving 253 cases 456,095 controls. Our results showed that lower stem cell factor (SCF) levels, basic fibroblast (bFGF) levels higher Interleukin-13 (IL-13) were associated with an increased risk (OR = 0.486, 95% CI 0.264-0.892, p 0.020; OR 0.323, 0.107-0.972, 0.044; 1.492, 1.111-2.004, 0.008, respectively). In addition, genetically predicted did not affect expression regulators. indicate play crucial Further studies are needed determine these biomarkers can be prevent treat

Language: Английский

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Causal relationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Oct. 29, 2022

Abstract Background Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear. Methods We performed a univariable multivariable Mendelian randomization study to evaluate associations. Genetic instruments exposures at the genome-wide significance level ( P < 5 × 10 –8 ) were selected from corresponding studies (n = 216,590 1,232,091 individuals). Summary-level data for BPH obtained UK Biobank (14,126 cases 169,762 non-cases) FinnGen consortium (13,118 72,799 non-cases). Results combined using fixed-effect meta-analysis. The odds ratios (ORs) 1.24 (95% confidence interval (CI), 1.07–1.43, 0.0045), 1.08 CI 1.01–1.17, 0.0175), 0.94 0.67–1.30, 0.6891), 1.29 0.88–1.89, 0.1922), 1.23 0.85–1.78, 0.2623), 1.04 0.76–1.42, 0.8165) one standard deviation (SD) increase waist BMI, relative carbohydrate, fat, protein sugar intake, 1.05 0.92–1.20, 0.4581) SD prevalence smoking initiation, 1.10 0.96–1.26, 0.1725) 0.84 0.69–1.02, 0.0741) log-transformed per day drinks week, 1.31 1.08–1.58, 0.0051) sedentary behavior. Genetically predicted circumference (OR 1.26, 95% 1.11–1.43, 0.0004) behavior 1.14, 1.05–1.23, 0.0021) after adjustment BMI. Conclusion This supports independent roles high BMI BPH.

Language: Английский

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Causal effects of gut microbiota on the risk of periodontitis: a two-sample Mendelian randomization study

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: May 25, 2023

Introduction The oral cavity and the gut tract are interconnected, both contain abundant natural microbiota. Gut microbiota may interact with flora participate in development of periodontitis. However, specific role certain taxa for periodontitis has not been investigated. Mendelian Randomization is an ideal method to explore causal relationships avoiding reverse causality potential confounding factors. Thus, we conducted a two-sample study comprehensively reveal genetic effect on Methods SNPs strongly associated 196 (18,340 individuals) were selected as instrument variables, (17,353 cases 28,210 controls) was used outcome. analyzed via random inverse variance-weighted, weighted median, MR-Egger. sensitivity analyses using Cochran’s Q tests, funnel plots, leave-one-out analyses, MR-Egger intercept tests. Results Nine ( Prevotella 7, Lachnospiraceae UCG-008, Enterobacteriales , Pasteurellales Enterobacteriaceae Pasteurellaceae Bacteroidales S24.7 group, Alistipes Eisenbergiella ) predicted play enhancing risk p &lt; 0.05). Besides, two Butyricicoccus Ruminiclostridium 6) have potentially inhibitive effects No significant estimation heterogeneity or pleiotropy detected. Conclusion Our demonstrates provides guidance clinical intervention

Language: Английский

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The association between sedentary behavior and obstructive sleep apnea: a cross-sectional study from the NHANES (2007–2008 to 2015–2020)

BMC Oral Health, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 12, 2024

Abstract Background Sedentary behavior (SB) may contribute to obesity and lower extremity fluid retention, which favor the development of obstructive sleep apnea (OSA). However, linking sedentary OSA is unclear. The purpose this study was determine if there an association between SB OSA. Methods Three typical questions in NHANES questionnaire(①The frequency feeling excessively sleepy per month. ②The gasping, snorting or stopping breathing week. ③The snoring week.) have been used for assessment A physical activity questionnaire(On a day, amount time you spend sitting reclining.) assess SB. This secondary analysis included National Health Nutrition Examination Survey (NHANES) participants (unweighted = 20,115). Weighted sample multiple logistic regression complex techniques were study. Results After adjustment confounders, with SB(> 8 h/d) had higher risk compared SB(< 4 h/d). Stratified by gender showed that no significant men. women, as reference, with(≥ increased By age-stratified analysis, stronger among older participants. Conclusion Analysis positive OSA, more pronounced women than 60 years old.

Language: Английский

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Physical activity lowers the risk for acute respiratory infections: Time for recognition

Journal of sport and health science/Journal of Sport and Health Science, Journal Year: 2022, Volume and Issue: 11(6), P. 648 - 655

Published: Aug. 20, 2022

Physical inactivity is a well-established risk factor for chronic diseases, such as cardiovascular disease, cancer, and diabetes mellitus. There growing awareness that physical should also be regarded acute respiratory infections (ARIs). ARIs, the common cold, influenza, pneumonia, coronavirus disease 2019 (COVID-19), are among most pervasive diseases on earth cause widespread morbidity mortality. Evidence in support of linkage between ARIs has been strengthened during COVID-19 pandemic because increased scientific scrutiny. Large-scale studies have consistently reported severe outcomes elevated cohorts with low activity and/or fitness, even after adjusting other factors. The lowered physically active groups attributed to exercise-induced immunoprotective effects, including enhanced surveillance key immune cells reduced inflammation. Scientific consensus groups, those who submitted Activity Guidelines Americans, not yet given this area research respect due. It time add "reduced ARIs" "Exercise Medicine" list activity-related health benefits.

Language: Английский

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Constipation and cardiovascular disease: A two-sample Mendelian randomization analysis

Frontiers in Cardiovascular Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 24, 2023

Although several observational studies have suggested positive associations between constipation and cardiovascular disease (CVD), a solid causal association has not been demonstrated. Therefore, two-sample Mendelian randomization (MR) study was performed to investigate the CVD.Independent genetic variants strongly associated with were obtained from FinnGen consortium. Summary-level data for CVD, including coronary artery (CAD), myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), stroke, its subtypes, collected few extensive genome-wide (GWASs). The inverse-variance weighted methods, median, MR-Egger used MR estimates. Cochran's Q test, intercept tests, MR-PRESSO, Steiger leave-one-out analyses, funnel plot in sensitivity analysis.Genetically determined suggestively AF risk (odds ratio (OR), 1.07; 95% confidence interval (CI), 1.01, 1.14; p = 0.016). Constipation other CVD do appear be causally related. It demonstrated that results robust through analyses.This suggestive of on AF, despite no achieving significance value after multiple testing corrections. There evidence an CAD, MI, HF, or stroke subtypes.

Language: Английский

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Causal association of leisure sedentary behavior and cervical spondylosis, sciatica, intervertebral disk disorders, and low back pain: a Mendelian randomization study

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: Jan. 23, 2024

Background Some studies suggest sedentary behavior is a risk factor for musculoskeletal disorders. This study aimed to investigate the potential causal association between leisure (LSB) (including television (TV) viewing, computer use, and driving) incidence of sciatica, intervertebral disk degeneration (IVDD), low back pain (LBP), cervical spondylosis (CS). Methods We obtained data LSB, CS, IVDD, LBP, sciatica proposed mediators from gene-wide (GWAS). The effects were examined by Inverse Variance Weighted (IVW) test, MR-Egger, weighted median, mode simple mode. And sensitivity analysis was performed using MR-Pleiotropy Residual Sum Outlier (MR-PRESSO) MR-Egger intercept test. Multivariable MR (MVMR) conducted independent other LSB; while two-step used explore including Body mass index (BMI), smoking initiation, type 2 diabetes mellitus (T2DM), major depressive disorder (MDD), schizophrenia, bipolar LSB these diseases based on previous studies. Results Genetically associated TV viewing positively with CS (OR = 1.61, 95%CI 1.25 2.07, p 0.002), IVDD 2.10, 1.77 2.48, 3.79 × 10 −18 ), LBP 1.84, 1.53 2.21, 1.04 −10 ) 1.82, 95% CI 1.45 2.27, 1.42 −7 ). While use reduced 0.66, 0.55 0.79, 8.06 −6 0.49, 0.40 0.59, 2.68 −13 0.58, 0.46 0.75, 1.98 −5 Sensitivity validated robustness outcomes. MVMR showed that effect 1.59, 1.13 2.25, 0.008), 2.15, 1.50 3.08, 3.38 1.03 2.52, 0.037) LSB. Furthermore, indicated BMI, T2DM may mediate diseases. Conclusion provides empirical evidence supporting positive which potentially mediated initiation T2DM.

Language: Английский

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Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 22, 2024

Objective The relationships between circulating inflammatory proteins and COVID-19 have been observed in previous cohorts. However, it is not unclear which may boost the risk of or protect against COVID-19. Methods We performed Mendelian randomization (MR) analysis using GWAS summary result 91 inflammation-related (N = 14,824) to assess their causal impact on severe phenotypes encompassed both hospitalized 2,095,324) critical 1,086,211). Moreover, sensitivity analyses were conducted evaluate robustness reliability. Results found that seven confer positive effects Among them, serum levels IL-10RB, FGF-19, CCL-2 positively contributed conditions (OR: 1.10~1.16), while other 4 conferred only 1.07~1.16), including EIF4EBP1, IL-7, NTF3, LIF. Meanwhile, five exert protective hospitalization progression 0.85~0.95), CXCL11, CDCP1, CCL4/MIP, IFNG, LIFR. Sensitivity did support presence heterogeneity majority MR analyses. Conclusions Our study revealed for COVID-19, vital implications treatment disease.

Language: Английский

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Potential causal associations between leisure sedentary behaviors, physical activity, sleep traits, and myopia: a Mendelian randomization study

BMC Ophthalmology, Journal Year: 2024, Volume and Issue: 24(1)

Published: March 5, 2024

Abstract Background Myopia is the most prevalent refractive error and a growing global health concern that significantly affects visual function. Researchers have recently emphasized considerably on influence of lifestyle myopia incidence development. This study investigates relationship between leisure sedentary behaviors (LSB)/physical activity (PA)/sleep traits myopia. Methods LSB, PA, sleep trait-associated genetic variants were used as instrument variables in Mendelian randomization (MR) to examine their causal effects Summary genome-wide association studies (GWASs) statistical data for LSB PA obtained from UK Biobank, was Biobank 23andMe, FinnGen. We summary statistics MRC IEU. The MR analyses performed using inverse variance-weighted (IVW), MR-Egger, weighted median, Pleiotropy RESidual Sum Outlier methods. Results Computer use genetically predicted increase risk [IVW odds ratio (OR) = 1.057; 95% confidence interval (CI), 1.038–1.078; P 7.04 × 10 − 9 ]. self-reported moderate-to-vigorous physical (MVPA) (IVW OR 0.962; CI, 0.932–0.993; 1.57 2 ) television watching 0.973; 0.961–0.985, 1.93 5 associated with lower risk. However, or accelerometer-measured had no significant associations Conclusion Our results indicated computer factor myopia, whereas MVPA may protect against These findings shed new light possible strategies reducing prevalence

Language: Английский

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Epidemiologic and genetic associations of female reproductive disorders with depression or dysthymia: a Mendelian randomization study

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 12, 2024

Abstract Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships different types of disorders remain unclear in terms direction magnitude. We conducted a comprehensive investigation using two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish relationship genetically predicted risk various pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), cysts, abnormal uterine vaginal bleeding(AUB), endometriosis, leiomyoma uterus, infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting pregnancy, cervical cancer, uterine/endometrial cancer. analyzed substantial sample size, ranging from 111,831 210,870 individuals, employed robust statistical methods, including inverse variance weighted, MR-Egger, weighted median, MR-PRESSO, estimate effects. Sensitivity analyses, Cochran's Q test, MR-Egger intercept leave-one-out funnel plots, were also ensure validity our results. Furthermore, factor analyses performed investigate potential mediators associated with these observed relationships. results demonstrated that genetic predisposition or dysthymia increased developing PCOS (OR = 1.43, 95% CI 1.28–1.59; P 6.66 × 10 –11 ), cysts 1.36, 1.20–1.55; 1.57 –6 AUB 1.41, 1.20–1.66; 3.01 –5 endometriosis 1.27–1.70; 2.21 –7 ) after Bonferroni correction, but no evidence for reverse causality. study did not find any supporting depression/dysthymia other In summary, provides specific findings emphasize importance management prevention treatment disorders, notably PCOS, AUB, endometriosis.

Language: Английский

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