Periodontitis and osteoporosis: a two-sample Mendelian randomization analysis

Abstract The incidences of periodontitis and osteoporosis are rising worldwide. Observational studies have shown that periodontitis is associated with increased risk of osteoporosis. We performed a Mendelian randomization (MR) study to genetically investigate the causality of periodontitis on osteoporosis. We explored the causal effect of periodontitis on osteoporosis by MR analysis. A total of 9 single nucleotide polymorphisms (SNP) were related to periodontitis. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, and penalized weighted median were used to analyze sensitivity. The fixed-effect IVW model and random-effect IVW model showed no significant causal effect of genetically predicted periodontitis on the risk of osteoporosis (OR=1.032; 95%CI: 0.923-1.153; P=0.574; OR=1.032; 95%CI: 0.920-1.158; P=0.588, respectively). Similar results were observed in simple mode (OR=1.031; 95%CI: 0.780-1.361, P=0.835), weighted mode (OR=1.120; 95%CI: 0.944-1.328, P=0.229), simple median (OR=1.003; 95%CI: 0.839-1.197, P=0.977), weighted median (OR=1.078; 95%CI: 0.921-1.262, P=0.346), penalized weight median (OR 1.078; 95%CI: 0.919-1.264, P=0.351), and MR-Egger method (OR=1.360; 95%CI: 0.998-1.853, P=0.092). There was no heterogeneity in the IVW and MR-Egger analyses (Q=7.454, P=0.489 and Q=3.901, P=0.791, respectively). MR-Egger regression revealed no evidence of a pleiotropic influence through genetic variants (intercept: -0.004; P=0.101). The leave-one-out sensitivity analysis indicated no driven influence of any individual SNP on the association between periodontitis and osteoporosis. The Mendelian randomization analysis did not show a significant detrimental effect of periodontitis on the risk of osteoporosis.

Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis: A Systematic Review / 生物医学与环境科学（英文）

OBJECTIVE@#This study explored the potentially modifiable factors for depression and major depressive disorder (MDD) from the MR-Base database and further evaluated the associations between drug targets with MDD.@*METHODS@#We analyzed two-sample of Mendelian randomization (2SMR) using genetic variant depression ( n = 113,154) and MDD ( n = 208,811) from Genome-Wide Association Studies (GWAS). Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes. The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD. Inverse variance weighted (IVW), fixed-effect inverse variance weighted (FE-IVW), MR-Egger, weighted median, and weighted mode were used for complementary calculation.@*RESULTS@#The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD. Also, the associations between drug targets and MDD showed that SLC6A4, GRIN2A, GRIN2C, SCN10A, and IL1B expression are associated with an increased risk of depression. In contrast, ADRB1, CHRNA3, HTR3A, GSTP1, and GABRG2 genes are candidate protective factors against depression.@*CONCLUSION@#This study identified the risk factors causally associated with depression and MDD, and estimated 10 drug targets with significant impact on MDD, providing essential information for formulating strategies to prevent and treat depression.

Application of Mendelian randomization in liver cancer / 临床肝胆病杂志

In recent years， the research method of Mendelian randomization based on genome-wide association studies has been widely used for etiological exploration in the medical field， which can effectively overcome the confounding biases and interference of reverse causalities in traditional observational researches with its unique advantages of the distributive randomness and timing priority of genetic variants. This article reviews the method of Mendelian randomization and its application in liver cancer， in order to provide new ideas for the research on causal association in liver cancer.

Casual Association Between Coffee Intake and Prostate Cancer Based on Two-sample Mendel Randomization / 肿瘤防治研究

Objective To assess the causal relationship between coffee intake and prostate cancer risk by using the two-sample Mendel randomization (MR) method. Methods The genome-wide association study (GWAS) data on coffee intake (exposure) and prostate cancer (outcome) were obtained from two independent data sets in UK Biobank. The inverse variance weighted method (IVW), weighted median estimator method (WME), and MR-Egger method were used for MR analyses. The OR value and 95%CI were used to represent the association between coffee intake and prostate cancer. In addition, the MR-Egger method was performed for pleiotropic and heterogeneity tests, and the leave-one-out method was used for sensitivity analysis. Results A total of 38 SNP were selected as instrumental variables. The IVW method showed that coffee intake might reduce the risk of prostate cancer (OR=0.994; 95%CI: 0.990-0.999; P=0.009). The WME method obtained the same conclusions (OR=0.991; 95%CI: 0.985-0.999; P=0.018), but MR-Egger regression did not find a causal relationship between coffee intake and prostate cancer (OR=0.992; 95%CI: 0.983-1.000; P=0.084). The MR-Egger method showed no pleiotropy (intercept=4.2E-5; P=0.581) or heterogeneity (Q=27.20; P=0.854) among the instrumental variables. The sensitivity analysis indicated that the conclusion was robust. Conclusion Two-sample Mendel randomization analysis reveals that coffee consumption might reduce the risk of prostate cancer.

Bidirectional casual effects between periodontitis and Sjögren's syndrome: a Mendelian randomization study / 口腔疾病防治

Objective@#To evaluate the bidirectional association between periodontitis and Sjögren's syndrome using the Mendelian randomization (MR) method.@*Methods@#Genome-wide association study (GWAS) data of periodontitis (N = 45 563) and Sjögren's syndrome (N = 214 435) were selected to meet the requirements of the same ethnicity and different regions. Inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) tests were used to evaluate the causal effect. Cochran's Q statistics, MR-Egger intercept, MR-PRESSO and leave-one-out analysis were used as sensitivity analyses to assess the stability and reliability of the results.@*Results@#After screening, the GWAS data of Sjögren's syndrome were based on the Finnish region, and the periodontitis GWAS data were based on the UK region, both of which originated from European ancestry. Using IVW (OR = 1.017, 95% CI = 0.956-1.082), MR-Egger (OR = 0.985, 95% CI= 0.956-1.082), and WM (OR =1.021, 95% CI = 0.948-1.099), no causal effect of Sjögren's syndrome on periodontitis was found using any of the three methods. Conversely, no causal effect of periodontitis on Sjögren's syndrome was found (IVW, OR = 1.024, 95% CI = 0.852-1.230; MR-Egger, OR = 0.978, 95% CI = 0.789-1.212; WM, OR = 1.024, 95% CI = 0.846-1.260). The sensitivity analyses indicated that the results were stable and reliable. Cochran's Q test and MR-PRESSO revealed that there was no significant heterogeneity among the instrumental variables, which included single nucleotide polymorphisms (SNPs). The intercept of MR-Egger regression indicated no pleiotropy in the included SNPs. No individual SNP was found that significantly affected the results using the leave-one-out method.@*Conclusion@#This study does not support a bidirectional causal effect between periodontitis and Sjögren's syndrome.

Research progress of Mendelian randomization in ocular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Etiological research is necessary for understanding the occurrence and epidemiological patterns of diseases, and is also a prerequisite for the diagnosis, prevention and treatment of clinical diseases. Mendelian randomization(MR), a method of research that combines genetics and epidemiology, has the advantage of exploring the causal relationship between exposure and disease genetically as well as avoiding confounding factors and reverse causation. Thus, it has been extensively utilized in the etiological study of diseases. This paper reviews the implementation of MR in the research of ocular diseases and provides ideas and approaches for the investigation of related mechanisms as well as the development of intervention strategies.

Association between ulcerative colitis and pancreatitis: a Mendelian randomization study / 预防医学

Objective @#To examine the causal relationship between ulcerative colitis (UC) and pancreatitis, to provide basis for early screening of pancreatitis among UC patients.@*Methods@#Genomic data of UC were obtained from 47 745 European individuals pooled by the International Inflammatory Bowel Disease Genetics Consortium, including 156 116 single nucleotide polymorphism (SNP), and genomic data of pancreatitis were obtained from 198 166 European individuals pooled from FinnGen, including 16 380 428 SNPs. Mendelian randomization (MR) analysis was performed using the inverse variance weighted (IVW) method with 72 UC-associated SNPs as instrumental variables and pancreatitis as the study outcome. The heterogeneity was assessed using Cochran Q test, the horizontal pleiotropy was assessed using MR-Egger regression, MR-PRESSO was performed with the exclusion of outliers, and effect of individual SNP on the results was tested with the leave-one-out method. @*Results@#MR analysis results showed that patients with genetically predicted UC had an increased risk of pancreatitis relative to those without UC (OR=1.076, 95%CI: 1.019-1.136, P<0.05). Cochran Q test showed no heterogeneity (P>0.05), and MR-Egger regression did not reveal horizontal pleiotropy of instrumental variables (P>0.05). The MR analysis results were robust after removing SNP one by one.@*Conclusions@#Genetically predicted UC is associated with an increased risk of pancreatitis. The screening for pancreatitis risk should be enhanced in patients with UC.

Application of Mendelian randomization analysis in exploring the etiology of nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） is an abnormal lipid metabolic disorder of the liver characterized by accumulation of a large amount of lipids in the liver， and it is currently the most common liver disease around the world. Mendelian randomization （MR） incorporates genomic data into traditional epidemiological study designs to infer the causal relationship between exposure factors and disease risk. In recent years， MR has been widely used in studies on inference of the etiology of NAFLD. This article systematically summarizes the advances in the application of MR in NAFLD research， so as to provide new ideas for understanding the nature of the disease and scientific interventions.

Association between the risk of increase in total cholesterol and the risk of cholelithiasis： A bidirectional Mendelian randomization study / 临床肝胆病杂志

ObjectiveTo investigate the association between the risk of increase in total cholesterol （TC） and the risk of cholelithiasis by using bidirectional Mendelian randomization （MR）. MethodsThe open gwas public database was used to obtain the single nucleotide polymorphism data associated with TC and cholelithiasis， and a secondary data analysis was performed for all summary data of genome-wide association studies. The genetic loci closely associated with TC or cholelithiasis were selected as exposure or outcome variables， and the bidirectional MR analysis was performed using the methods such as Egger regression， Weighted median， IVW random effects model， and IVW fixed effects model， with odds ratio （OR） values for evaluating the causal relationship between TC and cholelithiasis. ResultsWith TC as the exposure and cholelithiasis as the outcome， TC-cholelithiasis had an overall OR value of 0.91 （95% confidence interval ［CI］： 0.85‍ ‍—‍ ‍0.97） before elimination of heterogeneity and 0.93 （95%CI： 0.89‍ ‍—‍ ‍0.97） after elimination of heterogeneity. With cholelithiasis as the exposure and TC as the outcome， TC-cholelithiasis had an overall OR value of 0.20 （95%CI： 0.06‍ ‍—‍ ‍0.65） before elimination of heterogeneity and 0.28 （95%CI： 0.10‍ ‍—‍ ‍0.83） after elimination of heterogeneity. There was a bidirectional causal relationship between genetically predicted TC and cholelithiasis. ConclusionThis study confirms the bidirectional causal relationship between TC and cholelithiasis. The risk of cholelithiasis decreases with the increase in alleles associated with the elevation of TC level； on the contrary， the risk of elevated TC level decreases with the increase in alleles associated with the onset of cholelithiasis.

Effect of obesity, lipids and adipokines on allergic rhinitis risk: a Mendelian randomization study

Abstract Objectives: Observational studies suggested that obesity may promote the development of allergic rhinitis. The aim of this study was to explore the association of obesity, lipids and adipokines with this allergic disease at the genetic level using Mendelian randomization strategies. Methods: Summary data for three obesity indicators (such as body mass index), eight lipid indicators (such as triglycerides) and six adipokines (such as interleukin-6 and adipocyte fatty acid-binding protein) were collected, and suitable instrumental variables were extracted from these summary data according to the three main assumptions of Mendelian randomization. Three Mendelian randomization methods (such as inverse variance weighted) were used to detect the casual effect of the above indicators on allergic rhinitis risk. Sensitivity analyses were performed to assess heterogeneity and horizontal pleiotropy. Results: After Bonferroni correction, the inverse variance weighted reported that elevated levels of interleukin-6 and adipocyte fatty acid-binding protein were nominally associated with the decreased risk of allergic rhinitis (OR = 0.870, 95% CI 0.765-0.990, p = 0.035; OR = 0.732, 95% CI 0.551-0.973, p = 0.032). The other Mendelian randomization methods supported these results. Obesity, lipids and other adipokines were not related to this allergic disease. Sensitivity analyses found no heterogeneity and horizontal pleiotropy in the study. Conclusion: The study provided some interesting, but not sufficient, evidence to suggest that interleukin-6 and adipocyte fatty acid-binding protein might play a protective role in the development of allergic rhinitis at the genetic level. These findings should be validated by more research. Level of evidence: This was a Mendelian randomized study with a level of evidence second only to clinical randomized trials, and higher than cohort and case-control studies.

Análisis mediante variables instrumentales para establecer causalidad en investigaciones observacionales / Analysis through instrumental variables to establish causality in observational research

La identificación de relaciones causales es uno de los problemas fundamentales de la investigación científica en medicina y es necesaria para poder ejercerla en forma efectiva. Sin embargo, desde el punto de vista práctico es difícil establecer la existencia de relaciones causales en estudios de carácter observacional, en gran parte por la presencia de factores de confusión. El análisis a través de variables instrumentales es una de las estrategias que permite controlar el efecto confundidor y documentar la presencia de relaciones causa-efecto en estas situaciones. En este artículo, el autor resume los principales supuestos del análisis a través de variables instrumentales, haciendo foco en la aleatorización mendeliana. (AU)

The identification of causal relationships is one of the fundamental challenges in scientific research in medicine and is necessary for its effective practice. However, from a practical standpoint, establishing the existence of causal relationships in observational studies is difficult, largely due to the presence of confounding factors. Analysis through instrumental variables is one of the strategies that allows to control the confounding effect and documenting the presence of cause-and-effect relationships in these situations. In this article, the author summarizes the main assumptions of analysis through instrumental variables, with a focus on Mendelian randomization. (AU)

Causality between type 2 diabetes mellitus and age-related macular degeneration: a Mendelian randomization study / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the causality between type 2 diabetes mellitus(T2DM)and age-related macular degeneration(ARMD)based on two-sample Mendelian randomization(MR).METHODS: T2DM and ARMD samples were extracted from the FinnGen database. Inverse variance weighted(IVW)was used as the main analysis method, MR-Egger and weighted median(WM)as supplementary methods to analyze the potential relationship between them. In addition, Cochran Q test and MR-Egger intercept were also used to analyze the sensitivity, and the P-value was used as the index of research results.RESULTS: IVW showed that T2DM was associated with the incidence of exudative ARMD(OR=1.14, 95%CI 1.01～1.28, P=0.021), but it was not significantly associated with the incidence of atrophic ARMD(OR=0.96, 95%CI 0.86～1.07, P=0.554). The results of sensitivity analysis confirmed that there was no heterogeneity and pleiotropy in this study, and the results were reliable.CONCLUSION: There is a causal relationship between T2DM and exudative ARMD. Considering the high rate of blindness caused by ARMD, it is of great significance to recognize and control the risk factors of ARMD to reduce its prevalence rate and early diagnosis and treatment.

Causal relationship between branched-chain amino acids and peripheral atherosclerosis： a Mendelian randomization study / 上海预防医学

ObjectiveWe conducted a two-sample Mendelian randomization （MR） study to assess the causal relationship between circulating isoleucine， leucine and valine levels and the risk of peripheral atherosclerosis. MethodsBased on the large-scale genome-wide association study （GWAS） database， single nucleotide polymorphisms （SNPs） closely related to the circulating levels of isoleucine， leucine and valine were identified as instrumental variables （IVs）. Two-sample MR analysis applying the inverse variance weighted （IVW） method and the weighted median estimator （WME） method were performed to estimate the causal relationship between the risk of peripheral atherosclerosis and the exposure with more than three SNPs that were available as IVs. The pleiotropy was evaluated by using the MR-Egger regression and MR-PRESSO method， and the leave-one-out method was used in sensitivity analysis. ResultsFour， one and one SNPs were identified as IVs for circulating isoleucine， leucine and valine levels， respectively. For isoleucine， the IVW model demonstrated there was no evidence of heterogeneity among the IVs （P=0.715）， and there was a significant causal relationship between the increase of circulating isoleucine level and a higher risk of peripheral atherosclerosis risk. Per every 1 elevated standard deviation （SD） of circulating isoleucine level resulted in increasing 31% of peripheral atherosclerosis risk （OR=1.31， 95%CI： 1.07‒1.61）. Similarly， the OR（95%CI） was 1.33 （1.04‒1.71） in the WME model. The MR-Egger regression and MR-PRESSO analysis indicated no evidence of pleiotropy in IVs （all P>0.05）. The result of the leave-one-out sensitivity analysis was stable. The Wald ratio model displayed that the causal relationship between circulating leucine and valine levels and the risk of peripheral atherosclerosis was not statistically significant. The OR （95%CI） for leucine and valine was 1.13 （0.78‒1.63） and 1.11 （0.82‒1.50）， respectively. ConclusionThere is a significant causal relationship between the increase of circulating isoleucine level and a higher peripheral atherosclerosis risk. The causal relationships between circulating leucine and valine levels and the risk of peripheral atherosclerosis need to be further confirmed in future studies.

Genetically predicted insomnia causally increases the risk of erectile dysfunction / 亚洲男科学杂志(英文版)

Sleep has attracted extensive attention due to its significance in health. However, its association with erectile dysfunction (ED) is insufficiently investigated. To investigate the potential causal links between sleep traits (insomnia, sleep duration, and chronotype) and ED, this study was performed. The single-nucleotide polymorphisms (SNPs) associated with insomnia, sleep duration, and chronotype were retrieved from previous genome-wide association studies (GWAS). A conventional two-sample Mendelian randomization (MR) was used to estimate the causal links between sleep traits and ED. The summary statistics of ED were from individuals of European ancestry (6175 cases vs 217 630 controls). As shown by the random effect inverse-variance-weighting (IVW) estimator, genetically predicted insomnia was causally associated with a 1.15-fold risk of ED (95% confidence interval: 1.07-1.23, P < 0.001). Sleep duration and morningness were not causally associated with ED, as indicated by the IVW (all P > 0.05). These findings were consistent with the results of sensitivity analyses. Based on genetic data, this study provides causal evidence that genetically predicted insomnia increases the risk of ED, whereas sleep duration and chronotype do not.

Blood pressure phenotype, lipid fractions and type 2 diabetes: a trans-ethnic mendelian randomization study / 中华内分泌代谢杂志

Objective:To explore the causal associations of two blood pressure phenotype and four lipid fractions with type 2 diabetes mellitus(T2DM) in European and East Asian populations using Two-Sample Mendelian randomization analysis.Methods:Blood pressure phenotype, lipid fractions and T2DM genetic loci from two ethnics were matched and combined according to single nucleotide polymorphisms(SNPs) numbering. With SNPs closely related to the exposure phenotype as instrumental variables, the inverse variance weighting method was used to analyze the causal effects of blood pressure phenotype and lipid fractions on T2DM in different ethnic groups. The sensitivity analysis was conducted using MR-Egger regression model, Weighted Median method, MR-PRESSO, MR-robust Adjusted Profile Score, and leave-one-out method.Results:Among European populations, systolic blood pressure( OR=1.40, 95% CI 1.23-1.59, P<0.001) and diastolic blood pressure( OR =1.24, 95% CI 1.08-1.42, P=0.002)were associated with increased risk of T2DM while high density lipoprotein-cholesterol( OR=0.68, 95% CI 0.62-0.76, P<0.001) reduced the risk of T2DM. In East Asian ethnicity, elevated diastolic blood pressure( OR=0.75, 95% CI 0.59-0.95, P=0.007) reduced the risk of T2DM. Sensitivity analysis confirmed the results. Conclusion:There are differences in the effects of blood pressure phenotype and lipid composition on T2DM in different ethnic groups, which may be related to population heterogeneity and exposure sensitivity. It should be taken into consideration in extrapolation.

Association between gut microbiome and intracerebral hemorrhage based on genome-wide association study data / 中南大学学报(医学版)

OBJECTIVES@#Intracerebral hemorrhage (ICH) has the highest mortality and disability rates among various subtypes of stroke. Previous studies have shown that the gut microbiome (GM) is closely related to the risk factors and pathological basis of ICH. This study aims to explore the causal effect of GM on ICH and the potential mechanisms.@*METHODS@#Genome wide association study (GWAS) data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium. Based on the GWAS data, we first performed Mendelian randomization (MR) analysis to evaluate the causal association between GM and ICH. Then, a conditional false discovery rate (cFDR) method was conducted to identify the pleiotropic variants.@*RESULTS@#MR analysis showed that Pasteurellales, Pasteurellaceae, and Haemophilus were negatively correlated with the risk of ICH, whileVerrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae, Akkermansia, Holdemanella, and LachnospiraceaeUCG010 were positively correlated with ICH. By applying the cFDR method, 3 pleiotropic loci (rs331083, rs4315115, and rs12553325) were found to be associated with both GM and ICH.@*CONCLUSIONS@#There is a causal association and pleiotropic variants between GM and ICH.

Association of ticagrelor with risk of infection：a two-sample Mendelian randomization study based on the GWAS database / 中国药房

OBJECTIVE To investigate the causal association between ticagrelor and risk of infection METHODS Two-sample Mendelian randomization was adopted. Genetic instrumental variables were selected based on the results of the largest genome-wide association analysis to in vivo exposure of ticagrelor and its major active metabolite AR-C124910XX. The causal associations of ticagrelor and its major active metabolite AR-C124910XX with drug indications （coronary artery disease， unstable angina pectoris， myocardial infarction， stroke and ischemic stroke）were analyzed by inverse variance weighted Mendelian randomization model as a positive control for genetic instrumental variables. The causal relationship between ticagrelor and bacterial infection， acute lower respiratory infection， bacterial pneumoniae， pneumoniae，acute upper respiratory infection and sepsis were furtheranalyzed by using this method， and the robustness of the results was assessed by using heterogeneity tests and horizontal 202002030415） pleiotropy tests. RESULTS The increase of area under the curve at steady state （AUCss） of the genetic surrogated ticagrelor significantly reduced the risk of coronary artery disease， myocardial infarction and unstable angina pectoris （P＜0.001）. AUCss genetic instrument variables of its main active metabolite AR-C124910XX failed to pass positive control. Further analysis showed that the increase of the genetic surrogated ticagrelor exposure suggestively reduced the risk of bacterial infection [OR（95%CI）＝0.80（0.65，0.99），P＝0.040] and sepsis [OR （95%CI）＝0.84（0.73， 0.98）， P＝0.023]. The results of the heterogeneity tests showed that there was no heterogeneity in the causal association of the genetic surrogated ticagrelor AUCss with bacterial infection and sepsis （P＞0.05）. The results of horizontal pleiotropy tests showed that the causal association of genetic surrogated ticagrelor AUCss with bacterial infection and sepsis had no effects on horizontal pleiotropy （P＞0.05）. CONCLUSIONS Ticagrelor has a potential role in reducing the risk of sepsis and bacterial infections.

Causal Relationship Between Acromegaly and Colon Cancer: A Two-sample Mendelian Randomization Study / 肿瘤防治研究

Objective To determine the causal relationship between acromegaly and colon cancer by using two-sample Mendelian randomization. Methods Genetic loci closely related to acromegaly in the whole genome-wide association study (GWAS) were selected as tool variables, and the genetic data of colon cancer from different GWASs were analyzed by two-sample Mendelian randomization (MR).The inverse variance weighting method (IVW) of the random effect model was used for analysis, and MR-weighted median and MR-Egger methods were used to supplement the analysis. Results were presented as OR values. Results Four SNPs closely related to acromegaly were obtained as tool variables, and the multiplicity test of tool variables showed that P=0.59.Three methods were used to estimate causal effects.The IVW analysis were OR=1.00(0.99-1.001) and P=0.42;the MR-Egger analysis results were OR=1.00(0.99-1.001) and P=0.42;and the Weighted median analysis results were OR=1.00(1.00-1.001) and P=0.03.The sensitivity test showed that the confidence interval of the tool variable SNP passed through 0, indicating the robustness of the MR results. Conclusion Acromegaly is not an independent risk factor for colon cancer.

A mendelian randomization study of the causal association between gastroesophageal reflux and atrial fibrillation / 公共卫生与预防医学

Objective In this study，we performed two sampie Mendelian Randomization to infer a causal association between Gastroesophageal reflux(GERD) and Atrial fibrillation(AF)，it can effectively avoid the problems such as reverse causation and confounds in traditional epidemiology. Methods We used the Summary data of GERD and AF from published Genome wide association study(GWAS) of European Individuals. Single Nucleotide Polymorphisms (SNPs) were extracted as Instrumental Variables (IVs).The main MR methods include Inverse Variance [] Weighted(IVW)，Weighted Median(WME)，MR-Egger，Simple Mode，and Weighted Mode.In addition，we used the sensitivity analysis such as MR-PRESSO，Cochran's Q test etc. Results The IVW shows a causal association between GERD and AF(P<0.0001，OR=1.16，95%CI:1.10-1.23).The WME shows P＜0.0001，OR=1.20，95%CI:1.11-1.30；Simple Mode shows P=0.01，OR=1.34，95%CI:1.07-1.69；Weighted Mode shows P=0.02，OR=1.33，95%CI:1.06-1.66. Conclusion This study based on genetic data supports the causal association between GERD and AF. The occurrence of GERD could increase the risk of AF.

Mendelian randomization study to investigate the causal relationship between plasma homocysteine and chronic obstructive pulmonary disease / 世界急诊医学杂志（英文）

@#BACKGROUND: Several observational studies have shown an association between homocysteine (Hcy) levels and chronic obstructive pulmonary disease (COPD), but causal relationships are not clear. Our study aimed to explore the causal relationship between plasma Hcy and COPD by two-sample Mendelian randomization (MR). METHODS: A two-sample MR study was performed to infer the causal link. Genetically predicted plasma Hcy was selected as an instrumental variable (IV) from published genome-wide association study (GWAS) meta-analyses. COPD with different etiologies was extracted as outcome variables from other GWAS meta-analyses. The main MR analysis was performed using the inverse-variance weighted (IVW) method. Additional analyses were further performed using Cochran's Q-test and MR-Egger regression to evaluate the heterogeneity or horizontal pleiotropy of our findings. RESULTS: MR analysis showed no significant association between plasma Hcy and COPD. The results of the groups were consistent with the sensitivity analysis and repeated analysis, without heterogeneity or horizontal pleiotropy. The IVW results showed COPD hospital admissions (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.91-1.24, P=0.42), asthma/COPD (OR 0.97, 95% CI 0.89-1.06, P=0.55), COPD-related chronic infection (OR 1.50, 95% CI 0.57-3.99, P=0.41), COPD/asthma/interstitial lung disease (ILD)-related pneumonia or pneumonia-derived septicemia (OR 0.93, 95% CI 0.86-1.02, P=0.13), and COPD-related respiratory insufficiency (OR 1.00, 95% CI 0.7-1.44, P=0.99). CONCLUSION: There is no direct causal relationship between plasma Hcy and COPD in our study. As Hcy is known to have deleterious effects on endothelial function and vascular homeostasis, further studies are needed to investigate whether additional factors mediate the association between Hcy and COPD.