scholarly journals The Homocysteine and Metabolic Syndrome: A Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2440
Author(s):  
Ho-Sun Lee ◽  
Sanghwan In ◽  
Taesung Park
Keyword(s):  
Metabolic Syndrome ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Least Squares Regression ◽  
Causal Influence ◽  
The Metabolic Syndrome ◽  
Inverse Variance ◽  
Increased Risk ◽  
Weighted Median

Homocysteine (Hcy) is well known to be increased in the metabolic syndrome (MetS) incidence. However, it remains unclear whether the relationship is causal or not. Recently, Mendelian Randomization (MR) has been popularly used to assess the causal influence. In this study, we adopted MR to investigate the causal influence of Hcy on MetS in adults using three independent cohorts. We considered one-sample MR and two-sample MR. We analyzed one-sample MR in 5902 individuals (2090 MetS cases and 3812 controls) from the KARE and two-sample MR from the HEXA (676 cases and 3017 controls) and CAVAS (1052 cases and 764 controls) datasets to evaluate whether genetically increased Hcy level influences the risk of MetS. In observation studies, the odds of MetS increased with higher Hcy concentrations (odds ratio (OR) 1.17, 95%CI 1.12–1.22, p < 0.01). One-sample MR was performed using two-stage least-squares regression, with an MTHFR C677T and weighted Hcy generic risk score as an instrument. Two-sample MR was performed with five genetic variants (rs12567136, rs1801133, rs2336377, rs1624230, and rs1836883) by GWAS data as the instrumental variables. For sensitivity analysis, weighted median and MR–Egger regression were used. Using one-sample MR, we found an increased risk of MetS (OR 2.07 per 1-SD Hcy increase). Two-sample MR supported that increased Hcy was significantly associated with increased MetS risk by using the inverse variance weighted (IVW) method (beta 0.723, SE 0.119, and p < 0.001), the weighted median regression method (beta 0.734, SE 0.097, and p < 0.001), and the MR–Egger method (beta 2.073, SE 0.843, and p = 0.014) in meta-analysis. The MR–Egger slope showed no evidence of pleiotropic effects (intercept −0.097, p = 0.107). In conclusion, this study represented the MR approach and elucidates the significant relationship between Hcy and the risk of MetS in the Korean population.

The Metabolic SYNDROME and the RISK of Venous Thrombosis: RESULTS of AN Individual LEVEL Patient Meta-ANALYSIS

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3177-3177
Author(s):  
Francesco Dentali ◽  
Cihan Ay ◽  
Moon Jang ◽  
Matteo di Minno ◽  
Ingrid Pabinger ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Multivariate Analysis ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Visceral Obesity ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Individual Features ◽  
The Individual ◽  
The Impact

Abstract Abstract 3177 Background: The metabolic syndrome (MS) is a cluster of interrelated risk factors that identify patients at increased risk of cardiovascular events. Recent studies also suggested an association between MS and venous thromboembolism (VTE). However, the role of the individual features of MS and whether MS and its features are more important than obesity alone to predict VTE remain to be established. Methods: We performed an individual patient level meta-analysis of case-control studies comparing the prevalence of MS in patients with unprovoked VTE and in controls. MEDLINE, EMBASE databases, and abstract books were searched up to January 2010. Odds ratios (OR) and 95% confidence intervals of pooled results were calculated. The influence of individual variables (age, sex, BMI and MS) on the likelihood of VTE was compared using logistic regression analysis. Multivariate analysis was subsequently performed including the individual components of MS in the place of MS. The impact of increasing number of individual components of MS on the risk of VTE was investigated. Results: Four studies were identified and analyzed, for a total of 1332 patients (479 cases and 833 controls). Mean age was 53.3 and 52.7, respectively (p=n.s.), 49.5% cases and 42.4% controls were males (p=0.0003), 38.8% and 30.0% were obese (p=0.0001). MS was significantly associated with VTE (OR 1.97, 1.57–2.47), and the association linearly increased with the number of MS features (p for trend <0.001). At multivariate analysis, MS but not obesity remained associated with VTE (OR 1.92, 1.50–2.46 and 1.14, 0.88–1.47, respectively). All individual features of MS, but HDL cholesterol, were independently associated with VTE. Conclusions: The results of this meta-analysis confirm the association between MS and VTE and suggest that MS (and visceral obesity defined by increased waist circumference) could be a more important predictor of VTE than obesity defined by BMI. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Causal influence of dietary habits on the risk of major depressive disorder: a diet-wide Mendelian randomization analysis

2020 ◽  
Author(s):  
Tzu-Ting Chen ◽  
Chia-Yen Chen ◽  
Chiu-Ping Fang ◽  
Yen-Feng Lin
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Dietary Habits ◽  
Mendelian Randomization ◽  
P Value ◽  
Major Depressive ◽  
Causal Influence ◽  
Genome Wide ◽  
Inverse Variance ◽  
Weighted Median

Background Some evidence suggests that diet may potentially increase or decrease the risk of major depressive disorder (MDD). However, the association between dietary habits and MDD remains controversial. The aim of this study is to systemically investigate the causal influence of dietary habits on the risk of MDD by Mendelian randomization (MR) using diet-wide and genome-wide summary data. Methods To perform two-sample MR, we collected publicly available genome-wide association studies' summary statistics for dietary habits from GeneATLAS (n = 452,264) and MDD from Psychiatric Genomics Consortium (n = 43,204). We used a weighted median approach to synthesize MR estimates across genetic instruments. For the robustness of our results, we compared weighted median results with an inverse-variance weighted method, weighted mode method and MR-PRESSO. We also assessed the bidirectional relationships between dietary habits and major depressive disorder through bidirectional Mendelian randomization. Results Beef intake showed significant protective effects on MDD (β = -1.33; p-value = 0.002; Bonferroni-corrected p-value = 0.034; 11 single nucleotide polymorphisms [SNPs]), and cereal intake was nominally significantly protective (β = -0.15; p-value = 0.010; 51 SNPs). We obtained similar results by using an inverse-variance weighted method and weighted mode approach despite results in the weighted mode test being non-significant. We also found a potential effect of MDD on tea intake (β = 0.13; p-value = 0.021; 12 single SNPs). Conclusions In this two-sample MR, we observed that higher beef and cereal intake may be protective factors for MDD. We also found that MDD might trigger patients to drink more tea. Potential mechanisms need to be further investigated to support our novel findings.

scholarly journals Associations of sleep and circadian phenotypes with COVID-19 susceptibility and hospitalization: an observational cohort study based on the UK Biobank and a two-sample Mendelian randomization study

SLEEP ◽  
2022 ◽  
Author(s):  
Zheran Liu ◽  
Yaxin Luo ◽  
Yonglin Su ◽  
Zhigong Wei ◽  
Ruidan Li ◽  
...  
Keyword(s):  
Cohort Study ◽  
Excessive Daytime Sleepiness ◽  
Daytime Sleepiness ◽  
Mendelian Randomization ◽  
Causal Link ◽  
Uk Biobank ◽  
Inverse Variance ◽  
Increased Risk ◽  
Weighted Median ◽  
The Uk

Abstract Study Objectives Sleep and circadian phenotypes are associated with several diseases. The present study aimed to investigate whether sleep and circadian phenotypes were causally linked with coronavirus disease 2019 (COVID-19)-related outcomes. Methods Habitual sleep duration, insomnia, excessive daytime sleepiness, daytime napping, and chronotype were selected as exposures. Key outcomes included positivity and hospitalization for COVID-19. In the observation cohort study, multivariable risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated. Two-sample Mendelian randomization (MR) analyses were conducted to estimate the causal effects of the significant findings in the observation analyses. Beta values and the corresponding 95% CIs were calculated and compared using the inverse variance weighting, weighted median, and MR-Egger methods. Results In the UK Biobank cohort study, both often excessive daytime sleepiness and sometimes daytime napping were associated with hospitalized COVID-19 (excessive daytime sleepiness [often vs. never]: RR=1.24, 95% CI=1.02-1.5; daytime napping [sometimes vs. never]: RR=1.12, 95% CI=1.02-1.22). In addition, sometimes daytime napping was also associated with an increased risk of COVID-19 susceptibility (sometimes vs. never: RR= 1.04, 95% CI=1.01-1.28). In the MR analyses, excessive daytime sleepiness was found to increase the risk of hospitalized COVID-19 (MR IVW method: OR = 4.53, 95% CI = 1.04-19.82), whereas little evidence supported a causal link between daytime napping and COVID-19 outcomes. Conclusions Observational and genetic evidence supports a potential causal link between excessive daytime sleepiness and an increased risk of COVID-19 hospitalization, suggesting that interventions targeting excessive daytime sleepiness symptoms might decrease severe COVID-19 rate.

scholarly journals Genetic Studies of Metabolic Syndrome in Arab Populations: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zahrah Al-Homedi ◽  
Nariman Afify ◽  
Mashal Memon ◽  
Habiba Alsafar ◽  
Guan Tay ◽  
...  
Keyword(s):  
Systematic Review ◽  
Metabolic Syndrome ◽  
Genetic Association ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Small Scale ◽  
Odds Ratios ◽  
The Metabolic Syndrome ◽  
Increased Risk

Background: The metabolic syndrome (MetS) is prevalent in Arabian populations. Several small-scale studies have been performed to investigate the genetic basis of MetS. This systematic review and meta-analysis aimed to examine whether candidate gene polymorphisms are associated with MetS susceptibility among ethnic groups of the Arabian world and to suggest possible directions for future research regarding genetic markers and MetS.Methods: A search was conducted for peer-reviewed articles that examined the genetic association of MetS in Arabian populations in the following databases: Medline, Embase, Scopus, Direct Science, Web of Science, ProQuest, and Google Scholar until March 31, 2021. Articles were eligible if they were case-control studies, which investigated MetS as a dichotomous outcome (MetS vs no MetS). To assess the quality of the studies, the Q-Genie tool (Quality of Genetic Association Studies) was used. A non-central chi2 (random-effect) distribution was used to determine the heterogeneity (H) of Q and I (Galassi et al., The American journal of medicine, 2006, 119, 812–819) statistics.Results: Our search strategy identified 36 studies that met our inclusion criteria. In most cases, studies were excluded due to a lack of statistical information such as odds ratios, confidence intervals, and p-values. According to the Q-Genie tool, 12 studies scored poorly (a score of≤35), 13 studies scored moderately ( &gt;35 and≤45), and 12 studies had good quality ( &gt;45 or higher). The most frequently studied genes were FTO and VDR (both included in four studies). Three SNPs indicated increased risk for MetS after calculating the pooled odds ratios: FTO-rs9939609 (odds ratio 1.49, 95% CI: 0.96–2.32); LEP-rs7799039 (odds ratio 1.85, 95% CI: 1.37–2.5); and SERPINA12-rs2236242 (odds ratio 1.65, 95% CI: 1.21–2.24). Meta-analysis studies showed no significant heterogeneity.Conclusion: There were many sources of heterogeneity in the study settings. Most of the studies had low to moderate quality because of sample size and power issues, not considering all potential sources of bias, and not providing details about genotyping methods and results. As most studies were small-scale, aimed to replicate findings from other populations, we did not find any unique genetic association between MetS and Arabian populations.

Prevalence of metabolic syndrome in never treated mood disordered patientss

2007 ◽  
Vol 30 (4) ◽  
pp. 95
Author(s):  
Valerie Taylor ◽  
Glenda M. MacQueen
Keyword(s):  
Metabolic Syndrome ◽  
Mood Disorders ◽  
Population Attributable Risk ◽  
Disease Process ◽  
Visceral Obesity ◽  
Premature Mortality ◽  
Overweight And Obesity ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Bipolar Patients

Bipolar disorder and major depression are life-shortening illnesses. Unnatural causes such as suicide and accidents account for only a portion of this premature mortality1 Research is beginning to identify that mood disordered patients have a higher incidence of metabolic syndrome, an illness characterized by dyslipidemia, impaired glucose tolerance, hypertension and obesity.2 Metabolic syndrome is associated with an increased risk for a variety of physical illnesses. Hypothesis: Never treated patients with mood disorders have preexisting elevations in the prevalence of the component variables of metabolic syndrome. Central obesity will be especially elevated, predicting increased premature mortality. Methods: We assessed never treated patients with mood disorders for metabolic syndrome and its component variables. Patients were assessed at baseline and followed up at 6-month intervals. All psychiatric pharmacotherapy was documented. Body mass index (BMI) was also obtained and the percentage of deaths attributable to overweight and obesity was calculated using the population attributable risk (PAR). [PAR= ∑[P (RR-1)/RR] Results: Prior to the initiation of treatment, patients did not differ from population norms with respect to metabolic syndrome or BMI. At 2-year follow-up, BMI had increased for unipolar patients 2.02 points and 1.92 points for bipolar patients. (p < .001) This increase in BMI predicted an increase in mortality of 19.4%. Conclusion: An increase in visceral obesity is often the first component of metabolic syndrome to appear and may indicate the initiation of this disease process prematurely in this group. The increase in BMI places patients with mood disorders at risk for premature mortality and indicates a need for early intervention. References 1.Osby U, Brandt L, Correia N, Ekbom A & Sparen P. Excess mortability in bipolar and Unipolar disorder rin Sweden. Archives of General Psychiatry, 2001;58: 844-850 2.Toalson P, Saeeduddin A, Hardy T & Kabinoff G. The metabolic syndrome in patients with severe mental illness. Journal of Clinical Psychiatry, 2004; 6(4): 152-158

Metabolic Syndrome During Menopause

2019 ◽  
Vol 17 (6) ◽  
pp. 595-603 ◽  
Author(s):  
Sezcan Mumusoglu ◽  
Bulent Okan Yildiz
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Central Obesity ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Natural Menopause ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Aging Women

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.

ctDNA as a prognostic factor in operable colon cancer patients: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Emre Yekedüz ◽  
Elif Berna Köksoy ◽  
Hakan Akbulut ◽  
Yüksel Ürün ◽  
Güngör Utkan
Keyword(s):  
Colon Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Circulating Tumor Dna ◽  
Random Effects Model ◽  
Inverse Variance ◽  
Increased Risk ◽  
Significant Step ◽  
Tumor Dna

Aim: Using circulating tumor DNA (ctDNA) instead of historical clinicopathological factors to select patients for adjuvant chemotherapy (ACT) may reduce inappropriate therapy. Material & methods: MEDLINE was searched on March 31, 2020. Studies, including data related to the prognostic value of ctDNA in the colon cancer patients after surgery and after ACT, were included. The generic inverse-variance method with a random-effects model was used for meta-analysis. Results: Four studies were included for this meta-analysis. ctDNA-positive colon cancer patients after surgery and ACT had a significantly increased risk of recurrence compared with ctDNA-negative patients. Conclusions: ctDNA is an independent prognostic factor, and this meta-analysis is a significant step for using ctDNA instead of historical prognostic factors in the adjuvant setting.

Life Course Adiposity and Alzheimer’s Disease: A Mendelian Randomization Study

2021 ◽  
pp. 1-10
Author(s):  
Xian Li ◽  
Yan Tian ◽  
Yu-Xiang Yang ◽  
Ya-Hui Ma ◽  
Xue-Ning Shen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Course ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Fat Percentage ◽  
Regression Methods ◽  
Weighted Median

Background: Several studies showed that life course adiposity was associated with Alzheimer’s disease (AD). However, the underlying causality remains unclear. Objective: We aimed to examine the causal relationship between life course adiposity and AD using Mendelian randomization (MR) analysis. Methods: Instrumental variants were obtained from large genome-wide association studies (GWAS) for life course adiposity, including birth weight (BW), childhood body mass index (BMI), adult BMI, waist circumference (WC), waist-to-hip ratio (WHR), and body fat percentage (BFP). A meta-analysis of GWAS for AD including 71,880 cases and 383,378 controls was used in this study. MR analyses were performed using inverse variance weighted (IVW), weighted median, and MR-Egger regression methods. We calculated odds ratios (ORs) per genetically predicted standard deviation (1-SD) unit increase in each trait for AD. Results: Genetically predicted 1-SD increase in adult BMI was significantly associated with higher risk of AD (IVW: OR = 1.03, 95% confidence interval [CI] = 1.01–1.05, p = 2.7×10–3) after Bonferroni correction. The weighted median method indicated a significant association between BW and AD (OR = 0.94, 95% CI = 0.90–0.98, p = 1.8×10–3). We also found suggestive associations of AD with WC (IVW: OR = 1.03, 95% CI = 1.00–1.07, p = 0.048) and WHR (weighted median: OR = 1.04, 95% CI = 1.00–1.07, p = 0.029). No association was detected of AD with childhood BMI and BFP. Conclusion: Our study demonstrated that lower BW and higher adult BMI had causal effects on increased AD risk.

scholarly journals Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation

2021 ◽  
Author(s):  
Shuai Yuan ◽  
Maria Bruzelius ◽  
Susanna C. Larsson
Keyword(s):  
Renal Function ◽  
Venous Thromboembolism ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Genome Wide ◽  
Increased Risk ◽  
Mr Study

AbstractWhether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10−8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.

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