Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study

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

Published: May 13, 2022

Abstract Background The 2019 coronavirus disease pandemic (COVID-19) poses an enormous threat to public health worldwide, and the ensuing management of social isolation has greatly decreased opportunities for physical activity (PA) increased leisure sedentary behaviors (LSB). Given that both PA LSB have been established as major influencing factors obesity, diabetes cardiometabolic syndrome, whether PA/LSB in turn affects susceptibility COVID-19 by disrupting metabolic homeostasis remains be explored. In this study, we aimed systematically evaluate causal relationship between susceptibility, hospitalization severity using a Mendelian randomization study. Methods Data were obtained from large-scale dataset (N = 377,000), 422,218) Host Genetics Initiative 2,586,691). effects estimated with inverse variance weighted, MR-Egger, weighted median MR-PRESSO. Sensitivity analyses implemented Cochran’s Q test, MR-Egger intercept MR-PRESSO, leave-one-out analysis funnel plot. Risk factor further conducted investigate potential mediators. Results Genetically predicted accelerometer-assessed risk (OR 0.93, 95% CI 0.88–0.97; P 0.002), while television watching significantly 1.55, 1.29–1.88; 4.68 × 10 –6 ) 1.85, 1.33–2.56; 0.0002) after Bonferroni correction. No self-reported moderate vigorous (MVPA), accelerometer fraction accelerations > 425 milligravities, computer use or driving on progression observed. indicated above associations might mediated several factors, including smoking, high body mass index, elevated serum triglyceride levels, insulin resistance occurrence type 2 diabetes. Conclusion Our findings supported effect reduced well severity, which was potentially obesity diabetes-related phenotypes. Particular attention should given reducing encouraging proper exercise during quarantine COVID-19.

Language: Английский

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Causal effects of gut microbiota on the risk of chronic kidney disease: a Mendelian randomization study

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

Published: March 31, 2023

Background Previous studies have reported that gut microbiota is associated with an increased risk of chronic kidney disease (CKD) progression. However, whether has a causal effect on the development CKD not been revealed. Thus, we aimed to analyze potential using mendelian randomization (MR) study. Materials and Methods Independent single nucleotide polymorphisms closely 196 bacterial taxa (N = 18340) were identified as instrumental variables. Two-sample MR was performed evaluate 480698), including inverse-variance-weighted (IVW) method, weighted median MR-Egger, mode-based estimation MR-PRESSO. The robustness tested by series sensitivity analyses Cochran’s Q test, MR-Egger intercept analysis, leave-one-out analysis funnel plot. Statistical powers also calculated. Results genetically predicted higher abundance order Desulfovibrionales causally (odds ratio 1.15, 95% confidence interval: 1.05-1.26; p 0.0026). Besides, detected causalities between nine other ( Eubacterium eligens group , Desulfovibrionaceae Ruminococcaceae UCG-002 Deltaproteobacteria Lachnospiraceae UCG-010 Senegalimassilia Peptostreptococcaceae Alcaligenaceae Ruminococcus torques ) < 0.05). No heterogeneity or pleiotropy for significant estimates. Conclusion We found are CKD, thus confirming plays important role in pathogenesis CKD. Our work provides new indicators targets screening prevention

Language: Английский

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Large-scale genome-wide association studies reveal the genetic causal etiology between air pollutants and autoimmune diseases

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 29, 2024

Abstract Background Epidemiological evidence links a close correlation between long-term exposure to air pollutants and autoimmune diseases, while the causality remained unknown. Methods Two-sample Mendelian randomization (TSMR) was used investigate role of PM10, PM2.5, NO 2 , X (N = 423,796–456,380) in 15 diseases 14,890–314,995) using data from large European GWASs including UKB, FINNGEN, IMSGC, IPSCSG. Multivariable (MVMR) conducted direct effect each pollutant mediating common factors, body mass index (BMI), alcohol consumption, smoking status, household income. Transcriptome-wide association studies (TWAS), two-step MR, colocalization analyses were performed explore underlying mechanisms pollution diseases. Results In TSMR, after correction multiple testing, hypothyroidism causally associated with higher [odds ratio (OR): 1.37, p 9.08 × 10 –4 ] [OR: 1.34, 2.86 –3 ], ulcerative colitis (UC) 2.24, 1.23 –2 PM2.5 2.60, 5.96 rheumatoid arthritis 1.72, 1.50 systemic lupus erythematosus 4.92, 6.89 celiac disease lower 0.14, 6.74 0.17, 3.18 ]. The risky effects on UC significant MVMR adjusting for other pollutants. revealed several mediators Transcriptional analysis identified specific gene transcripts pathways interconnecting Two-step MR that POR, HSPA1B, BRD2 might mediate POR pQTL (rs59882870, PPH4=1.00) strongly colocalized Conclusion This research underscores necessity rigorous surveillance within public health curb prevalence Graphical abstract (Built by Biorender)

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 < 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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Causal effects of COVID-19 on structural changes in specific brain regions: a Mendelian randomization study

BMC Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 19, 2023

Abstract Background Previous studies have found a correlation between coronavirus disease 2019 (COVID-19) and changes in brain structure cognitive function, but it remains unclear whether COVID-19 causes structural which specific regions are affected. Herein, we conducted Mendelian randomization (MR) study to investigate this causal relationship identify vulnerable COVID-19. Methods Genome-wide association (GWAS) data for phenotypes (28,900 cases 3,251,161 controls) were selected as exposures, GWAS traits (cortical thickness surface area from 51,665 participants volume of subcortical structures 30,717 participants) outcomes. Inverse-variance weighted method was used the main estimate method. The median, MR-Egger, MR-PRESSO global test, Cochran’s Q statistic detect heterogeneity pleiotropy. Results genetically predicted infection phenotype nominally associated with reduced cortical caudal middle frontal gyrus ( β = − 0.0044, p 0.0412). hospitalized lateral orbitofrontal 0.0049, 0.0328) rostral 0.0022, 0.0032) well temporal 10.8855, 0.0266). These relationships also identified severe phenotype. Additionally, cuneus 0.0024, 0.0168); pericalcarine 2.6628, 0.0492), superior parietal 5.6310, 0.0408), parahippocampal 0.1473, 0.0297); hippocampus 15.9130, 0.0024). Conclusions Our indicates suggestively significant genetic predisposition atrophy functional human brain. Patients impairment should be actively managed alleviate neurocognitive symptoms minimize long-term effects.

Language: Английский

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Causal relationship between multiple sclerosis and cortical structure: a Mendelian randomization study

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 20, 2024

Abstract Background Observational studies have suggested an association between multiple sclerosis (MS) and cortical structure, but the results been inconsistent. Objective We used two-sample Mendelian randomization (MR) to assess causal relationship MS structure. Methods data as exposure trait, including 14,498 cases 24,091 controls, were obtained from International Multiple Sclerosis Genetics Consortium. Genome-wide study (GWAS) for surface area (SAw/nw) thickness (THw/nw) in 51,665 individuals of European ancestry ENIGMA The inverse-variance weighted (IVW) method was primary analysis MR. Sensitivity analyses conducted evaluate heterogeneity pleiotropy. Enrichment performed on MR filtered by sensitivity analysis. Results After IVW filtering, only six surviving provided suggestive evidence supporting a lingual SAw ( p = .0342, beta (se) 5.7127 (2.6969)), parahippocampal .0224, 1.5577 (0.6822)), rostral middle frontal .0154, − 9.0301 (3.7281)), cuneus THw .0418, 0.0020 (0.0010)), lateral orbitofrontal .0281, 0.0025 THnw .0417, 0.0029 (0.0014)). that leukocyte cell-related pathways, JAK-STAT signaling pathway, NF-kappa B cytokine-cytokine receptor interaction, prolactin pathway may be involved effect morphology. Conclusion Our provide suggests pathways mediating brain morphology abnormalities patients are mainly related immune inflammation-driven pathways.

Language: Английский

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Preliminary study of the effect of gut microbiota on the development of prostatitis

BMC Medical Genomics, Journal Year: 2024, Volume and Issue: 17(1)

Published: Jan. 25, 2024

Abstract Background Dysbacteriosis of intestinal tract may cause systemic inflammation, making distant anatomical locations more susceptible to illness. Recent research has demonstrated that the microbiome can affect both prostatitis and inflammation prostate is linked cancer. It still unclear, though, whether this relationship indicates causation. We conducted a Mendelian randomization investigation on two samples fully uncover gut microbiota’s potential genetic causal role in prostatitis. Method Prostatitis (1859 cases 72,799 controls) was utilized as outcome, while SNPs highly with 196 microbial taxa (18 340 people) were chosen instrumental factors. Random effects, inverse variance weighting, weighted medians, MR-Egger used analyze effects. The Cochran’s Q test, funnel plot, leave-one-out analysis, intercept test all sensitivity analysis. Results A effect lowering incidence anticipated for five microorganisms ( Methanobacteria , Methanobacteriaceae Erysipelatoclostridium Parasutterella Slackia ; P < 0.05). Four bacteria, including Faecalibacterium LachnospiraceaeUCG004 Sutterella Gastranaerophilales are predicted play increasing risk There no discernible estimates pleiotropy or heterogeneity. Conclusion Our established links between nine prostatitis, which offer fresh perspectives theoretical framework future prevention management

Language: Английский

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Causal association of sarcopenia-related traits with brain cortical structure: a bidirectional Mendelian randomization study

Aging Clinical and Experimental Research, Journal Year: 2025, Volume and Issue: 37(1)

Published: Feb. 27, 2025

Abstract Background Patients with sarcopenia often experience cognitive decline, affecting cortical structures, but the causal link remains unclear. We used bidirectional Mendelian randomization (MR) to explore relationship between sarcopenia-related traits and structure. Methods selected genetic variables from genome-wide association study data. Three different MR methods were used: inverse-variance weighted analysis, MR-Egger regression, median test. For significant estimates, we further conducted Cochran’s Q test, intercept leave-one-out analyses, MR-PRESSO assess heterogeneity. Results In forward appendicular lean mass (ALM) decreased thickness (TH) of lateral occipital gyrus increased TH pars opercularis (β = -0.0079 mm, 95% CI: -0.0117 mm -0.0041 P < 0.0001; β 0.0080 0.0042 0.0117 0.0001). reverse a negative correlation was found bankssts ALM, while positive correlations observed frontal pole, rostral anterior cingulate, temporal ALM. The pole positively correlated right hand grip strength (HGS-R) 0.1596 0.1349 0.1843 0.0001), triangularis left-hand (HGS-L) 0.3251 0.2339 0.4163 Conclusions Sarcopenia-related structure have effects, supporting muscle-brain axis theory. This links neurocognitive diseases provides new strategies for prevention intervention both decline.

Language: Английский

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Causal Association Between Tea Consumption and Kidney Function: A Mendelian Randomization Study

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: March 29, 2022

Background Causal research concerning the consumption of tea and risk chronic kidney disease (CKD) is limited. This study identified potential causal effects intake on CKD, estimated glomerular filtration rate (eGFR), albuminuria. Methods Genome-wide association studies (GWASs) from UK Biobank were able to identify single-nucleotide polymorphisms (SNPs) associated with an extra cup each day. The summary statistics for function CKDGen consortium include 11,765 participants (12,385 cases CKD) 54,116 urinary albumin-to-creatinine ratio who mostly European descent. A two-sample Mendelian randomization (MR) analysis was performed test relationship between selected SNPs CKD. Results total 2,672 ( p &lt; 5 × 10 –8 ) found, 45 which independent usable in CKDGen. Drinking more cups per day indicates a protective effect CKD G3-G5 [odds (OR) = 0.803; 0.004] increases eGFR (β 0.019 log ml/min/1.73 m 2 day; 2.21 –5 ). Excluding two responsible directional heterogeneity (Cochran Q 0.02), high also negatively correlated lower albuminuria (OR 0.758; 0.002). Conclusion From perspective genes, relationships exist daily reduced increased eGFR.

Language: Английский

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Psychiatric disorders and Type 2 diabetes mellitus: A bidirectional Mendelian randomization

European Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 53(3)

Published: Oct. 19, 2022

Extensive observational evidence put forward the association between psychiatric disorders and type 2 diabetes mellitus (T2DM). However, causal relationships these two diseases required further research. Thus, we evaluated bidirection casual effect five T2DM using two-sample mendelian randomization (MR).By selecting single nucleotide polymorphisms associated with (attention-deficit hyperactivity disorder (ADHD), major depressive (MDD), schizophrenia, anxiety panic disorder), a bidirectional MR was applied to evaluate causality diseases. The inverse-variance weighted (IVW) method used as primary analysing approach for estimating possible effects. MR-Egger median were also conducted verify results. funnel plot, Cochran's Q test intercept sensitivity analyses. In addition, potential mediators investigated by risk factor analyses.Genetic susceptibilities of ADHD MDD would increase (ADHD: OR = 1.14, 95%CI 1.08-1.20; p=5.7×10-6 ; MDD: 1.22, 1.09-1.36; p=0.0004 ). genetic predisposition (OR 1.09, 1.04-1.14; p 0.0004). Several factors implicated in above associations, including smoking, high body mass index, waist-to-hip ratio elevated serum triglycerides.Our studies indicated on increasing T2DM, which potentially mediated smoking obesity-related phenotypes. Meanwhile, found ADHD. prevention strategies should include mental health vice versa.

Language: Английский

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