Association Between Obesity and Cardiovascular Outcomes: A Systematic Review and Meta-analysis of Mendelian Randomization Studies. Riaz Haris,Khan Muhammad Shahzeb,Siddiqi Tariq Jamal,Usman Muhammad Shariq,Shah Nishant,Goyal Amit,Khan Sadiya S,Mookadam Farouk,Krasuski Richard A,Ahmed Haitham JAMA network open Importance:Although dyslipidemia has been consistently shown to be associated with atherogenesis, an association between obesity and cardiovascular disease outcomes remains controversial. Mendelian randomization can minimize confounding if variables are randomly and equally distributed in the population of interest. Objective:To assess evidence from mendelian randomization studies to provide a less biased estimate of any association between obesity and cardiovascular outcomes. Data Sources:Systematic searches of MEDLINE and Scopus from database inception until January 2018, supplemented with manual searches of the included reference lists. Study Selection:Studies that used mendelian randomization methods to assess the association between any measure of obesity and the incidence of cardiovascular events and those that reported odds ratios (ORs) with 95% CIs estimated using an instrumental variable method were included. The 5 studies included in the final analysis were based on a consensus among 3 authors. Data Extraction and Synthesis:Two investigators independently extracted study characteristics using a standard form and pooled data using a random-effects model. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Main Outcomes and Measures:Obesity associated with type 2 diabetes, coronary artery disease, or stroke. The hypothesis was formulated prior to data collection. Results:Of 4660 potentially relevant articles, 2511 titles were screened. Seven studies were included in the systematic review, and 5 studies with 881 692 participants were eligible to be included in the meta-analysis. Pooled estimates revealed that obesity was significantly associated with an increased risk of type 2 diabetes (OR, 1.67; 95% CI, 1.30-2.14; P < .001; I2 = 93%) and coronary artery disease (OR, 1.20; 95% CI, 1.02-1.41; P = .03; I2 = 87%). No association between obesity and stroke was found (OR, 1.02; 95% CI, 0.95-1.09; P = .65; I2 = 0%). Conclusions and Relevance:The present meta-analysis suggests that obesity is associated with type 2 diabetes and coronary artery disease. Although this analysis of mendelian randomization studies does not prove causality, it is supportive of a causal association. Hence, health care practitioners should continue to emphasize weight reduction to combat coronary artery disease. 10.1001/jamanetworkopen.2018.3788

Association between genetically determined telomere length and health-related outcomes: A systematic review and meta-analysis of Mendelian randomization studies. Aging cell Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta-analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health-related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR-Egger, weighted median, MR-PRESSO, and multivariate MR. Meta-analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non-GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta-analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length. 10.1111/acel.13874

Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study. BMC medicine BACKGROUND:Several recent observational studies have reported that gut microbiota composition is associated with preeclampsia. However, the causal effect of gut microbiota on preeclampsia-eclampsia is unknown. METHODS:A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis (n=13,266) conducted by the MiBioGen consortium. The summary statistics of preeclampsia-eclampsia were obtained from the FinnGen consortium R7 release data (5731 cases and 160,670 controls). Inverse variance weighted, maximum likelihood, MR-Egger, weighted median, weighted model, MR-PRESSO, and cML-MA were used to examine the causal association between gut microbiota and preeclampsia-eclampsia. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be causally associated with preeclampsia-eclampsia in forward Mendelian randomization analysis. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. RESULTS:Inverse variance weighted estimates suggested that Bifidobacterium had a protective effect on preeclampsia-eclampsia (odds ratio = 0.76, 95% confidence interval: 0.64-0.89, P = 8.03 × 10). In addition, Collinsella (odds ratio = 0.77, 95% confidence interval: 0.60-0.98, P = 0.03), Enterorhabdus (odds ratio = 0.76, 95% confidence interval: 0.62-0.93, P = 8.76 × 10), Eubacterium (ventriosum group) (odds ratio = 0.76, 95% confidence interval: 0.63-0.91, P = 2.43 × 10), Lachnospiraceae (NK4A136 group) (odds ratio = 0.77, 95% confidence interval: 0.65-0.92, P = 3.77 × 10), and Tyzzerella 3 (odds ratio = 0.85, 95% confidence interval: 0.74-0.97, P = 0.01) presented a suggestive association with preeclampsia-eclampsia. According to the results of reverse MR analysis, no significant causal effect of preeclampsia-eclampsia was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. CONCLUSIONS:This two-sample Mendelian randomization study found that Bifidobacterium was causally associated with preeclampsia-eclampsia. Further randomized controlled trials are needed to clarify the protective effect of probiotics on preeclampsia-eclampsia and their specific protective mechanisms. 10.1186/s12916-022-02657-x

Mendelian Randomization Studies of Lifestyle-Related Risk Factors for Osteoarthritis: A PRISMA Review and Meta-Analysis. International journal of molecular sciences Risk factors for osteoarthritis (OA) often exert effects over protracted time-courses. Mendelian randomization (MR) studies therefore have an advantage over conventional observational studies when studying the causal effect of long-term lifestyle-related risk factors on OA. However, given the heterogeneous design of existing MR studies on OA, the reported causal estimates of these effects remain inconsistent, thus obscuring the true extent of the biological effects of OA lifestyle-risk factors. We conducted a PRISMA systematic review and specifically included MR studies that investigated the causal effect between lifestyle-related risk factors and OA, where causal estimates for various lifestyle factors were pooled for meta-analysis. Quality of studies was assessed according to STROBE-MR guidelines. A total of 1576 studies were evaluated and 23 were included. Overall, the studies included were of high quality and had a low risk of bias. Our meta-analysis demonstrates the positive causal effect of BMI (OR 1.49 [1.23-1.80]) and negative causal effects of serum calcium (OR 0.69 [0.57-0.83]) and LDL levels (OR 0.93 [0.90-0.96]) on OA. Despite the heterogeneous designs and estimates of causal effects provided by various MR studies, our meta-analysis suggests that lifestyle-related risk factors in the form of BMI, serum calcium, and LDL have true biological effects on the development of OA. 10.3390/ijms231911906

The association between human papillomavirus and bladder cancer: Evidence from meta-analysis and two-sample mendelian randomization. Journal of medical virology INTRODUCTION:Bladder cancer (BCa) is the 10th most common type of cancer worldwide, and human papillomavirus (HPV) is the most common sexually transmitted infection. However, the relationship between HPV infection and the risk of BCa is still controversial and inconclusive. METHODS:This systematic review and meta-analysis were conducted following the PRISMA 2020 reporting guideline. This study searched four bibliographic databases with no language limitation. The databases included PubMed (Medline), EMBASE, Cochrane Library, and Web of Science. Studies evaluating the interaction between HPV infection and the risk of BCa from inception through May 21, 2022, were identified and used in this study. This study estimated the overall and type-specific HPV prevalence and 95% confidence intervals (95% CI) using Random Effects models and Fixed Effects models. In addition, this study also calculated the pooled odds ratio and pooled risk ratio with 95% CI to assess the effect of HPV infection on the risk and prognosis of bladder cancer. Two-sample mendelian randomization (MR) study using genetic variants associated with HPV E7 protein as instrumental variables were also conducted. RESULTS:This study retrieved 80 articles from the four bibliographic databases. Of the total, 27 were case-control studies, and 53 were cross-sectional studies. The results showed that the prevalence of HPV was 16% (95% CI: 11%-21%) among the BCa patients, most of which were HPV-16 (5.99% [95% CI: 3.03%-9.69%]) and HPV-18 (3.68% [95% CI: 1.72%-6.16%]) subtypes. However, the study found that the prevalence varied by region, detection method, BCa histological type, and sample source. A significantly increased risk of BCa was shown for the positivity of overall HPV (odds ratio [OR], 3.35 [95% CI: 1.75-6.43]), which was also influenced by study region, detection method, histological type, and sample source. In addition, the study found that HPV infection was significantly associated with the progression of BCa (RR, 1.73 [95% CI: 1.39-2.15]). The two-sample MR analysis found that both HPV 16 and 18 E7 protein exposure increased the risk of BCa (HPV 16 E7 protein: IVW OR per unit increase in protein level = 1.0004 [95% CI: 1.0002-1.0006]; p = 0.0011; HPV 18 E7 protein: IVW OR per unit increase in protein level = 1.0003 [95% CI: 1.0001-1.0005]; p = 0.0089). CONCLUSION:In conclusion, HPV may play a role in bladder carcinogenesis and contribute to a worse prognosis for patients with BCa. Therefore, it is necessary for people, especially men, to get vaccinated for HPV vaccination to prevent bladder cancer. 10.1002/jmv.28208