Association between inflammatory bowel disease and cancer risk: evidence triangulation from genetic correlation, Mendelian randomization, and colocalization analyses across East Asian and European populations.

BACKGROUND: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), has been associated with several cancer risks in observational studies, but the observed associations have been inconsistent and may face the bias of confounding and reverse causality. The potential causal relationships between IBD and the risk of cancers remain largely unclear. METHODS: We performed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analyses using summary genome-wide association study (GWAS) data across East Asian and European populations to evaluate the causal relationships between IBD and cancers. Sensitivity analyses for the MR approach were additionally performed to explore the stability of the results. RESULTS: There were no significant genetic correlations between IBD, CD, or UC and cancers (all P values > 0.05) in East Asian or European populations. According to the main MR analysis, no significant causal relationship was observed between IBD and cancers in the East Asian population. There were significant associations between CD and ovarian cancer (odds ratio [OR] = 0.898, 95% CI = 0.844-0.955) and between UC and nonmelanoma skin cancer (OR = 1.002, 95% CI = 1.000-1.004, P = 0.019) in the European population. The multivariable MR analysis did not find any of the above significant associations. There was no shared causal variant to prove the associations of IBD, CD, or UC with cancers in East Asian or European populations using colocalization analysis. CONCLUSIONS: We did not provide robust genetic evidence of causal associations between IBD and cancer risk. Exposure to IBD might not independently contribute to the risk of cancers, and the increased risk of cancers observed in observational studies might be attributed to factors accompanying the diagnosis of IBD.

Associations of metabolic changes and polygenic risk scores with cardiovascular outcomes and all-cause mortality across BMI categories: a prospective cohort study.

BACKGROUND: Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories. METHODS: In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m2, 25 ≤ BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories. RESULTS: During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (Pinteraction < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed. CONCLUSIONS: MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved.

Genome-Wide Mapping of Plasma IgG N-Glycan Quantitative Trait Loci Identifies a Potentially Causal Association between IgG N-Glycans and Rheumatoid Arthritis.

Observational studies highlight associations of IgG N-glycosylation with rheumatoid arthritis (RA); however, the causality between these conditions remains to be determined. Standard and multivariable two-sample Mendelian randomization (MR) analyses integrating a summary genome-wide association study for RA and IgG N-glycan quantitative trait loci (IgG N-glycan-QTL) data were performed to explore the potentially causal associations of IgG N-glycosylation with RA. After correcting for multiple testing (p < 2 × 10-3), the standard MR analysis based on the inverse-variance weighted method showed a significant association of genetically instrumented IgG N-glycan (GP4) with RA (odds ratioGP4 = 0.906, 95% confidence interval = 0.857-0.958, p = 5.246 × 10-4). In addition, we identified seven significant associations of genetically instrumented IgG N-glycans with RA by multivariable MR analysis (p < 2 × 10-3). Results were broadly consistent in sensitivity analyses using MR_Lasso, MR_weighted median, MR_Egger regression, and leave-one-out analysis with different instruments (all p values <0.05). There was limited evidence of pleiotropy bias (all p values > 0.05). In conclusion, our MR analysis incorporating genome-wide association studies and IgG N-glycan-QTL data revealed that IgG N-glycans were potentially causally associated with RA. Our findings shed light on the role of IgG N-glycosylation in the development of RA. Future studies are needed to validate our findings and to explore the underlying physiological mechanisms in the etiology of RA.

Bidirectional Two-Sample Mendelian Randomization Study of Immunoglobulin G N-Glycosylation and Senescence-Associated Secretory Phenotype.

Observational studies revealed changes in Immunoglobulin G (IgG) N-glycosylation during the aging process. However, it lacks causal insights and remains unclear in which direction causal relationships exist. The two-sample bidirectional Mendelian randomization (MR) design was adopted to explore causal associations between IgG N-glycans and the senescence-associated secretory phenotype (SASP). Inverse variance weighted (IVW) and Wald ratio methods were used as the main analyses, supplemented by sensitivity analyses. Forward MR analyses revealed causal associations between the glycan peak (GP) and SASP, including GP6 (odds ratio [OR] = 0.428, 95% confidence interval [CI] = 0.189-0.969) and GP17 (OR = 0.709, 95%CI = 0.504-0.995) with growth/differentiation factor 15 (GDF15), GP19 with an advanced glycosylation end-product-specific receptor (RAGE) (OR = 2.142, 95% CI = 1.384-3.316), and GP15 with matrix metalloproteinase 2 (MMP2) (OR = 1.136, 95% CI =1.008-1.282). The reverse MR indicated that genetic liability to RAGE was associated with increased levels of GP17 (OR = 1.125, 95% CI = 1.003-1.261) and GP24 (OR = 1.222, 95% CI = 1.046-1.428), while pulmonary and activation-regulated chemokines (PARC) exhibited causal associations with GP10 (OR = 1.269, 95% CI = 1.048-1.537) and GP15 (OR = 1.297, 95% CI = 1.072-1.570). The findings provided suggested evidence on the bidirectional causality between IgG N-glycans and SASP, which might reveal potential regulatory mechanisms.

The Causality between Human Immunoglobulin G (IgG) N-Glycosylation and Aging: A Mendelian Randomization Study.

BACKGROUND: Immunoglobulin G (IgG) N-glycosylation is considered a potential biomarker for aging and various pathological conditions. However, whether these changes in IgG N-glycosylation are a consequence or a contributor to the aging process remains unclear. This study aims to investigate the causality between IgG N-glycosylation and aging using Mendelian randomization (MR) analysis. METHODS: We utilized genetic variants associated with IgG N-glycosylation traits, the frailty index (FI), and leukocyte telomere length (LTL) from a previous genome-wide association study (GWAS) on individuals of European ancestry. Two-sample and multivariable MR analyses were conducted, employing the inverse-variance weighted (IVW) method. Sensitivity analyses were performed to assess potential confounding factors. RESULTS: Using the IVW method, we found suggestive evidence of a causal association between GP14 and FI (ß 0.026, 95% CI 0.003 to 0.050, p = 0.027) and LTL (ß -0.020, 95% CI -0.037 to -0.002, p = 0.029) in the two-sample MR analysis. In the multivariable MR analysis, suggestive evidence was found for GP23 and FI (ß -0.119, 95% CI -0.219 to -0.019, p = 0.019) and GP2 and LTL (ß 0.140, 95% CI 0.020 to 0.260, p = 0.023). CONCLUSIONS: In conclusion, our results supported a potentially causal effect of lower GP23 levels on an advanced aging state. Additional verification is required to further substantiate the causal relationship between glycosylation and aging.

Nanofiber-based wound dressing in wound healing of elderly patients.

Introduction: With the aging of the population, it has become a serious problem that the wounds of elderly patients are not easy to heal. Aim: To explore the application of nanofiber wound dressing in wound healing of elderly patients. Material and methods: In this article, 86 elderly patients with chronic wounds admitted to the Affiliated Hospital of Shaanxi University of Chinese Medicine from January 2023 to September 2023 were enrolled, and they were randomly divided into control and experimental groups, with 43 cases in each group. Controls used traditional wound dressings in care. The experimental group used nanofiber wound dressings. The wound healing efficacy, inflammatory factors, side effects, wound infection degree, healing time, and pain were compared between the two groups. Results: The total effective rate of the experimental group (97.67%) was higher as against controls (86.04%). Wound germiculture positive (7.14 ±2.76%) was lower in the experimental group as against controls (22.13 ±3.27%. The wound healing time of the experimental group (18.68 ±5.78 d) was shorter as against controls (30.24 ±6.19 d). The visual analogue scale (VAS) score of the experimental group (2.68 ±0.41 s) was lower as against controls (3.57 ±0.89 s) after 16 days of care (p < 0.05). Conclusions: The use of nanofiber dressings is an effective means to promote wound healing in elderly patients, which is worthy of application in practical care.

Time spent in a better cardiovascular health and risk of cardiovascular diseases and mortality: a prospective cohort study.

BACKGROUND: The protective effect of a higher ideal cardiovascular health (CVH) score on cardiovascular diseases (CVDs) and mortality is well recognized. However, little is known regarding the length of favorable CVH status associated with CVDs and mortality. This study aimed to examined whether the duration of better (ideal or intermediate) CVH is associated with risk of developing CVDs and mortality. METHODS: This prospective cohort study used data from 83,536 individuals from 2006 to 2020 who were enrolled in the Kailuan Study. The CVH scores of individuals were assessed at visits 1, 2, 3, and 4, respectively. The years spent in better CVH were estimated for each individual as the number of examination cycles (0-4) in which the participant was in that CVH score ≥ 8 multiplied by 2 (the mean year interval of each visit). The primary outcomes are CVD events and all-cause mortality. RESULTS: After a median follow-up period of 7.48 years, 5486 (7.07%) cases of incident CVD events and 7669 (9.18%) deaths occurred. Compared with participants in " ≤ 4 years" group, those who maintained for > 4 years had less likely to develop adverse outcomes (CVD events: hazard ratio (HR): 0.60, 95% confidence interval (CI 0.56-0.63; all-cause mortality: HR: 0.77, 95% CI 0.74-0.81). The number of years spent in better CVH was nonlinearly correlated with CVD events or mortality (all Ps for nonlinear < 0.05). The results indicated that maintaining more than 6 years in a better CVH status was associated with a decreased risk of CVD events or mortality. CONCLUSION: Our study indicates that individuals maintaining more than 6 years in better CVH could increase cardiometabolic benefits and a lower risk of all-cause mortality.

Genetic association and causal inference between lung function and venous thromboembolism.

BACKGROUND: Previous studies have indicated that lower lung function is related to a higher risk of venous thromboembolism (VTE). However, causal inferences may be affected by confounders, coheritability or reverse causality. We aimed to explore the causal association between lung function and VTE. METHODS: Summary data from public genome-wide association studies (GWAS) for lung function and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly related to exposure were filtered as proxy instruments. We adopted linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomization (MR) analyses to infer the genetic backgrounds and causal associations between different lung functions and VTE events. RESULTS: LDSC showed a genetic correlation between forced expiratory volume in one second (FEV1) and deep vein thrombosis (DVT) (rg = - 0.189, P = 0.005). In univariate MR (UVMR), there was suggestive evidence for causal associations of genetically predicted force vital capacity (FVC) with DVT (odds ratio (OR) 0.774; 95% confidence interval (CI) 0.641-0.934) via forwards analysis and genetically predicted pulmonary embolism (PE) with FVC (OR 0.989; 95% CI 0.979-0.999) via reverse analysis. Multivariate MR (MVMR) analyses of lung function-specific SNPs suggested no significant direct effects of lung function on VTE, and vice versa. Of note is the borderline causal effect of PE on FEV1 (OR 0.921; 95% CI 0.848-1.000). CONCLUSIONS: Our findings identified a coheritability of FEV1 (significant) and FVC (suggestive) with DVT. There was no convincing causal relationship between lung function and the risk of VTE events. The borderline causal effect of PE on FEV1 and the significant genetic correlation of FEV1 with DVT may have clinical implications for improving the quality of existing prevention and intervention strategies.

Unravelling the genetic causality of immunoglobulin G N-glycans in ischemic stroke.

BACKGROUND: Evidence suggests that immunoglobulin G (IgG) N-glycosylation is associated with ischemic stroke (IS). However, the causality of IgG N-glycosylation for IS remains unknown. METHODS: Two-sample Mendelian randomization (MR) analyses were performed to investigate the potential causal effects of genetically determined IgG N-glycans on IS using publicly available summarized genetic data from East Asian and European populations. Genetic instruments were used as proxies for IgG N-glycan traits. IgG N-glycans were analysed using ultra-performance liquid chromatography. Four complementary MR methods were performed, including the inverse variance weighted method (IVW), MR‒Egger, weighted median and penalized weighted median. Furthermore, to further test the robustness of the results, MR based on Bayesian model averaging (MR-BMA) was then applied to select and prioritize IgG N-glycan traits as risk factors for IS. RESULTS: After correcting for multiple testing, in two-sample MR analyses, genetically predicted IgG N-glycans were unrelated to IS in both East Asian and European populations, and the results remained consistent and robust in the sensitivity analysis. Moreover, MR-BMA also showed consistent results in both East Asian and European populations. CONCLUSIONS: Contrary to observational studies, the study did not provide enough genetic evidence to support the causal associations of genetically predicted IgG N-glycan traits and IS, suggesting that N-glycosylation of IgG might not directly involve in the pathogenesis of IS.

Effects of polyunsaturated fatty acids serum levels on vascular dementia: A two-sample Mendelian randomization study.

INTRODUCTION: Several observational studies have indicated that polyunsaturated fatty acids serum levels (PUFAs) are associated with vascular dementia (VaD), but their causal relationships remain elusive. Therefore, we attempted to evaluate the causal effect of PUFAs on VaD in a two-sample Mendelian randomization (MR) analysis by using summary statistics from aggregated genome-wide association studies. METHODS: The inverse-variance weighted (IVW) method was performed as the primary analysis. Sensitivity analyses (MR-Egger regression, weighted median, penalized weighted median and MR pleiotropy residual sum and outlier methods) were also implemented to estimate the effects of potential violations of MR hypotheses. RESULTS: No causality was found for PUFAs (OR, 1.14; 95% CI, .91-1.42; p = .25) on VaD in the IVW model. The results were consistent in sensitivity analyses. There was no notable horizontal pleiotropy or heterogeneity. CONCLUSION: In this two-sample MR analysis, our findings did not support the assumption that PUFAs play causal role in the occurrence or development of VaD.

Causality assessment of circulating Vitamin D level on venous thromboembolism: A Mendelian randomization study.

BACKGROUND AND AIMS: The associations of vitamin D level with venous thromboembolism (VTE) reported in observational studies, whereas these causal associations were uncertain in European population. Therefore, we used Mendelian randomization (MR) method to explore the causal associations between 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of VTE and its subtypes [including deep vein thrombosis (DVT) and pulmonary embolism (PE)]. METHODS AND RESULTS: We used three kinds of genetic instruments to proxy the exposure of 25(OH)D, including genetic variants significantly associated with 25(OH)D, expression quantitative trait loci of 25(OH)D target genes, and genetic variants within or nearby 25(OH)D target genes. MR analyses did not provide any evidence for the associations of 25(OH)D levels with VTE and its subtypes (p > 0.05). The summary-data-based MR (SMR) analyses indicated that elevated expression of VDR was associated with decreased risk of VTE (OR = 0.81; 95% CI, 0.65-0.998; p = 0.047) and PE (OR = 0.67; 95% CI, 0.50-0.91; p = 0.011), and expression of AMDHD1 was associated with PE (OR = 0.93; 95% CI, 0.88-0.99; p = 0.027). MR analysis provided a significant causal effect of 25(OH)D level mediated by gene AMDHD1 on PE risk (OR = 0.09; 95% CI, 0.01-0.60; p = 0.012). CONCLUSION: Our MR analysis did not support causal association of 25(OH)D level with the risk of VTE and its subtypes. In addition, the expression of VDR and AMDHD1 involved in vitamin D metabolism showed a strong association with VTE or PE and might represent targets for these conditions.

Immunoglobulin G N-glycan, inflammation and type 2 diabetes in East Asian and European populations: a Mendelian randomization study.

BACKGROUND: Immunoglobulin G (IgG) N-glycans have been shown to be associated with the risk of type 2 diabetes (T2D) and its risk factors. However, whether these associations reflect causal effects remain unclear. Furthermore, the associations of IgG N-glycans and inflammation are not fully understood. METHODS: We examined the causal associations of IgG N-glycans with inflammation (C-reactive protein (CRP) and fibrinogen) and T2D using two-sample Mendelian randomization (MR) analysis in East Asian and European populations. Genetic variants from IgG N-glycan quantitative trait loci (QTL) data were used as instrumental variables. Two-sample MR was conducted for IgG N-glycans with inflammation (75,391 and 18,348 participants of CRP and fibrinogen in the East Asian population, 204,402 participants of CRP in the European population) and T2D risk (77,418 cases and 356,122 controls of East Asian ancestry, 81,412 cases and 370,832 controls of European ancestry). RESULTS: After correcting for multiple testing, in the East Asian population, genetically determined IgG N-glycans were associated with a higher risk of T2D, the odds ratios (ORs) were 1.009 for T2D per 1- standard deviation (SD) higher GP5, 95% CI = 1.003-1.015; P = 0.0019; and 1.013 for T2D per 1-SD higher GP13, 95% CI = 1.006-1.021; P = 0.0005. In the European population, genetically determined decreased GP9 was associated with T2D (OR = 0.899 per 1-SD lower GP9, 95% CI: 0.845-0.957). In addition, there was suggestive evidence that genetically determined IgG N-glycans were associated with CRP in both East Asian and European populations after correcting for multiple testing, but no associations were found between IgG N-glycans and fibrinogen. There was limited evidence of heterogeneity and pleiotropy bias. CONCLUSIONS: Our results provided novel genetic evidence that IgG N-glycans are causally associated with T2D.

Moderate physical activity may not decrease the risk of cardiovascular disease in persistently overweight and obesity adults.

BACKGROUND: Body mass index (BMI) and physical activity (PA) has been documented to be associated with cardiovascular disease (CVD). However, the evidences regarding joint phenotypes of BMI and PA trajectories with risk for CVD and all-cause mortality are still limited. METHODS: Participants from the Kailuan Study, followed up during 2006-2019 were included, with primary outcomes of CVDs (myocardial infarction or stroke) and all-cause mortality. BMI and PA were repeatedly measured at least three times, and thus joint phenotypes trajectory groups were identified by group-based trajectory modeling. Cox proportional hazards models were used to examine the associations between trajectory groups and CVDs and all-cause mortality. RESULTS: Totally 88,141 (6 trajectories) and 89,736 participants (5 trajectories) were included in the final analyses relating trajectories to CVDs and all-cause mortality, respectively. Compared with persistent normal-weight with moderate PA group, participants were associated with increased risk of CVD in persistent overweight with moderate PA trajectory group (adjusted hazard ratio [aHR]: 1.31, 95% confidence interval [CI]: 1.22-1.41) and persistent obesity with moderate PA trajectory group (aHR: 1.55, 95% CI: 1.41-1.69). While the rising to overweight with moderate PA in normal-weight status with active PA (aHR: 0.72, 95% CI: 0.65-0.79), persistent overweight with moderate PA (aHR: 0.92, 95% CI: 0.87-0.97) and decline to normal-weight in overweight status with moderate PA (aHR: 0.73, 95% CI: 0.67-0.80) trajectories group were significantly associated with decreased all-cause mortality risk. The associations remained robust among stratifying by age and sex individuals and sensitive analysis. CONCLUSIONS: The long-term trajectories analysis showed that moderate PA may not decrease the risk of CVD in persistently overweight and obesity adults.

Machine learning of plasma metabolome identifies biomarker panels for metabolic syndrome: findings from the China Suboptimal Health Cohort.

BACKGROUND: Metabolic syndrome (MetS) has been proposed as a clinically identifiable high-risk state for the prediction and prevention of cardiovascular diseases and type 2 diabetes mellitus. As a promising "omics" technology, metabolomics provides an innovative strategy to gain a deeper understanding of the pathophysiology of MetS. The study aimed to systematically investigate the metabolic alterations in MetS and identify biomarker panels for the identification of MetS using machine learning methods. METHODS: Nuclear magnetic resonance-based untargeted metabolomics analysis was performed on 1011 plasma samples (205 MetS patients and 806 healthy controls). Univariate and multivariate analyses were applied to identify metabolic biomarkers for MetS. Metabolic pathway enrichment analysis was performed to reveal the disturbed metabolic pathways related to MetS. Four machine learning algorithms, including support vector machine (SVM), random forest (RF), k-nearest neighbor (KNN), and logistic regression were used to build diagnostic models for MetS. RESULTS: Thirteen significantly differential metabolites were identified and pathway enrichment revealed that arginine, proline, and glutathione metabolism are disturbed metabolic pathways related to MetS. The protein-metabolite-disease interaction network identified 38 proteins and 23 diseases are associated with 10 MetS-related metabolites. The areas under the receiver operating characteristic curve of the SVM, RF, KNN, and logistic regression models based on metabolic biomarkers were 0.887, 0.993, 0.914, and 0.755, respectively. CONCLUSIONS: The plasma metabolome provides a promising resource of biomarkers for the predictive diagnosis and targeted prevention of MetS. Alterations in amino acid metabolism play significant roles in the pathophysiology of MetS. The biomarker panels and metabolic pathways could be used as preventive targets in dealing with cardiometabolic diseases related to MetS.

Optical determination of layered-materials InSe thickness via RGB contrast method and regression analysis.

Indium selenide (InSe) features intriguing thickness-dependent optoelectronic properties, and a simple, and precise way to identify the thickness is essential for the rapid development of InSe research. Here, a red, green, and blue (RGB) color contrast method with regression analysis for quantitative correlation of three optical contrasts from RGB channels with the InSe thickness (1-35 nm), is demonstrated. The lower accuracy of the thickness identification obtained from the individual channels was discussed. Moreover, the effective refractive indices in the three RGB regions can be extracted from the Fresnel equation and numerical analysis by finding the best fit to the experimental optical contrast. After further consideration of the wavelength-dependent refractive indices, the slope of the regression line between the estimated thickness and that obtained from the atomic force microscope was improved from 1.59 ± 0.05 to 0.97 ± 0.02. The complex refractive index spectra of InSe (1-10 layers) generated fromab initionumerical calculation results were also adopted to identify the InSe thickness. Compared to dispersion, the evolution of the band structure had less effect on thickness identification. This work could be extended to other layered materials, facilitate the thickness-dependent study of layered materials, and expedite the realization of their practical applications.

Vascular endothelial growth factor and the risk of venous thromboembolism: a genetic correlation and two-sample Mendelian randomization study.

BACKGROUND: The relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE. METHODS: Summary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score regression (LDSC) and five robust MR analytical approaches were conducted to estimate the genetic correlations and causal inference. The MR-Egger intercept, Cochran's Q, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on outcomes. Notably, replication analyses were performed using different subgroups of VTE. RESULTS: LDSC failed to identify genetic correlations between VEGF and VTE. Based on 9 SNPs, the circulating VEGF level was positively related to the risk of VTE using inverse variance weighting (IVW) method (odds ratio (OR) = 1.064, 95% confidence interval (CI), 1.009-1.122). Reverse MR analyses showed that genetic liability for VTE was not associated with increased VEGF level (ß = -0.021, 95% CI, -0.087-0.045). Pleiotropy-robust methods indicated no bias in any estimates. CONCLUSIONS: Our findings failed to detect coheritability between VEGF and VTE. The suggestive positive effect of the higher VEGF level on the VTE risk may have clinical implications, suggesting that VEGF as a possible predictor and therapeutic target for VTE prevention need to be further warranted.

Causal associations between COVID-19 and atrial fibrillation: A bidirectional Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies showed that coronavirus disease (2019) (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). The causal association between COVID-19 infection or its severity and susceptibility of atrial fibrillation (AF) remains unknown. METHODS AND RESULTS: The bidirectional causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with not hospitalized COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and AF are determined by using two-sample Mendelian randomization (MR) analysis. Genetically predicted severe COVID-19 was not significantly associated with the risk of AF [odds ratio (OR), 1.037; 95% confidence interval (CI), 1.005-1.071; P = 0.023, q = 0.115]. In addition, genetically predicted AF was also not causally associated with severe COVID-19 (OR, 0.993; 95% CI, 0.888-1.111; P = 0.905, q = 0.905). There was no evidence to support the association between genetically determined COVID-19 and the risk of AF (OR, 1.111; 95% CI, 0.971-1.272; P = 0.127, q = 0.318), and vice versa (OR, 1.016; 95% CI, 0.976-1.058; P = 0.430, q = 0.851). Besides, no significant association was observed for hospitalized COVID-19 with AF. MR-Egger analysis indicated no evidence of directional pleiotropy. CONCLUSION: Overall, this MR study provides no clear evidence that COVID-19 is causally associated with the risk of AF.

Protocol of the Inner Mongolian Healthy Aging Study (IMAGINS): a longitudinal cohort study.

BACKGROUND: Cardiovascular diseases (CVDs) remain the leading cause of premature mortality and burden of diseases in the world. The Inner Mongolia Autonomous Region is located in northern China, constitute 17.66% individuals with Mongolian, which have unique diet and lifestyles. Therefore, the Inner Mongolian Healthy Aging Study (IMAGINS) was designed to explore risk factors for chronic diseases and evaluate the effectiveness of health management on CVDs in population at high-risk. METHODS: The IMAGINS is an ongoing and prospective cohort study of men and women aged ≥35 years from Inner Mongolian Autonomous Region, northern China. This study performed in investigating risk factors for CVDs, screening and providing health management strategy for high-risk population of CVDs. The IMAGINS began in September 2015 and scheduled to recruiting and follow-up outcome until 2030. For general population, a long-term follow-up will be conducted every 5 years to collect the information above and data on clinical outcomes. For high-risk population, comprehensive health managements were performed and scheduled to follow-up annually. All IMAGINS participants are followed for incident CVDs and death. DISCUSSION: The IMAGINS is designed to increase understanding how cardiovascular-related risk factors contribute to the development of CVDs and the positive effect of health management strategy for high-risk CVD participants. Key features of this study include (i) a carefully characterized cohort between high risk of CVDs and non-high risk population; (ii) detailed measurement of CVDs risk factors and health management strategies for high risk population; (iii) long-term follow-up of CVDs and death. The IMAGINS represents a good research opportunity to investigate clinical and genetic factors in high-risk population, might providing basis for the prevention and control of non-communicable diseases.

Construct validity of the Suboptimal Health Status Questionnaire-25 in a Ghanaian population.

BACKGROUND: The Suboptimal Health Status Questionnaire-25 (SHS-Q-25) developed to measure Suboptimal Health Status has been used worldwide, but its construct validity has only been tested in the Chinese population. Applying Structural Equation Modelling, we investigate aspects of the construct validity of the SHS-Q-25 to determine the interactions between SHS subscales in a Ghanaian population. METHODS: The study involved healthy Ghanaian participants (n = 263; aged 20-80 years; 63% female), who responded to the SHSQ-25. In an exploratory factor and parallel analysis, the study extracted a new domain structure and compared to the established five-domain structure of SHSQ-25. A confirmatory factor analysis (CFA) was conducted and the fit of the model further discussed. Invariance analysis was carried out to establish the consistency of the instrument across multi-groups. RESULTS: The extracted domains were reliable with Cronbach's [Formula: see text] of 0.846, 0.820 and 0.864 respectively, for fatigue, immune-cardiovascular and cognitive. The CFA revealed that the model fit indices were excellent [Formula: see text]. The fit indices for the three-domain model were statistically superior to the five-domain model. There were, however, issues of insufficient discriminant validity as some average variance extracts were smaller than the corresponding maximum shared variance. The three-domain model was invariant for all constrained aspects of the structural model across age, which is an important risk factor for most chronic diseases. CONCLUSION: The validity tests suggest that the SHS-Q25 can measure SHS in a Ghanaian population. It can be recommended as a screening tool to early detect chronic diseases especially in developing countries where access to facilities is diminished.

Association between high-density lipoprotein cholesterol and type 2 diabetes mellitus among Chinese: the Beijing longitudinal study of aging.

BACKGROUND: Some previous studies on different populations have yielded inconsistent findings with respect to the relationship between levels of high-density lipoprotein cholesterol (HDL-C) and future type 2 diabetes mellitus (T2DM) incidence. This study was designed to gain further insight into this relationship through a cohort study with a 25-year follow-up duration. METHODS: In total, 1462 individuals that were 55 years of age or older and were free of T2DM at baseline were enrolled in the present study. T2DM incidence among this study population was detected through self-reported diagnoses or the concentration of fasting plasma glucose. The data were derived from nine surveys conducted from 1992 to 2017. The correlation between HDL-C levels and the T2DM risk was assessed through Cox proportional-hazards model and proportional hazards model for the sub-distribution with time-dependent variables. RESULTS: Over the follow-up period, 120 participants were newly diagnosed with new-onset T2DM. When research participants were separated into four groups on the basis for quartiles of their levels of HDL-C measured at baseline, and incidence of diabetes declined with higher baseline HDL-C levels at 12.60, 9.70, 5.38, and 5.22 per 1000 person-years, respectively. Adjusted hazard ratios (HRs) were 0.98 (95% confidence interval [CI]: 0.62-1.55), 0.48 (95% CI: 0.27-0.85) and 0.44 (95% CI: 0.25-0.80) for individuals with HDL-C levels within the 1.15-1.39, 1.40-1.69, and ≥ 1.70 mmol/L ranges relative to participants with HDL-C levels < 1.15 mmol/L. Multiple sensitivity analyses similarly revealed reduced risk of diabetes incidence with increased HDL-C levels. Incorporating the levels of HDL-C into a multivariate model significantly enhanced the overall power of the predictive model (P values were 0.0296, 0.0011, respectively, for 5- and 10-year risk of diabetes). CONCLUSIONS: Levels of HDL-C were independently and negatively associated with the risk of the new-onset T2DM among middle-aged and elderly Chinese.