Extending the MR-Egger method for multivariable Mendelian randomization to correct for both measured and unmeasured pleiotropy.
paper
Cited
Public
- Authors
- Rees, Jessica M B; Wood, Angela M; Burgess, Stephen
- Year
- 2017
- Journal
- Statistics in medicine
- PMID
- 28960498
- DOI
- 10.1002/sim.7492
- PMCID
- PMC5725762
Methods have been developed for Mendelian randomization that can obtain consistent causal estimates while relaxing the instrumental variable assumptions. These include multivariable Mendelian randomization, in which a genetic variant may be associated with multiple risk factors so long as any association with the outcome is via the measured risk factors (measured pleiotropy), and the MR-Egger (Mendelian randomization-Egger) method, in which a genetic variant may be directly associated with the outcome not via the risk factor of interest, so long as the direct effects of the variants on the outcome are uncorrelated with their associations with the risk factor (unmeasured pleiotropy). In this paper, we extend the MR-Egger method to a multivariable setting to correct for both measured and unmeasured pleiotropy. We show, through theoretical arguments and a simulation study, that the multivariable MR-Egger method has advantages over its univariable counterpart in terms of plausibility of the assumption needed for consistent causal estimation and power to detect a causal effect when this assumption is satisfied. The methods are compared in an applied analysis to investigate the causal effect of high-density lipoprotein cholesterol on coronary heart disease risk. The multivariable MR-Egger method will be useful to analyse high-dimensional data in situations where the risk factors are highly related and it is difficult to find genetic variants specifically associated with the risk factor of interest (multivariable by design), and as a sensitivity analysis when the genetic variants are known to have pleiotropic effects on measured risk factors.
Causal directed acyclic graph illustrating univariable Mendelian randomization assumptions with potential violation of IV3 by a pleiotropic effect indicated by a dotted line. The genetic effect of G j on X is βXj, the direct (pleiotropic) effect of G j on Y via an independent pathway is α j (representing the potential violation of the IV3 assumption), and the causal effect of the risk factor X on the outcome Y is θ. U represents the set of variables that confound the association between X and Y
LLM interpretation
This is a causal directed acyclic graph (DAG) illustrating univariable Mendelian randomization assumptions. It shows a primary causal pathway from a genetic variant ($G_j$) to a risk factor ($X$) with effect $\beta_{X_j}$, and from $X$ to an outcome ($Y$) with effect $\theta$, while $U$ represents confounding variables affecting both $X$ and $Y$. A dotted line labeled $\alpha_j$ indicates a potential violation of the IV3 assumption via a direct pleiotropic effect from $G_j$ to $Y$.
Causal directed acyclic graph illustrating multivariable Mendelian randomization assumptions for a set of genetic variants G j, 3 risk factors X 1, X 2, and X 3, and outcome Y. The genetic effect of G j on X k is βXkj, the direct (pleiotropic) effect of G j on Y is αj′, and the causal effect of the risk factor X k on the outcome Y is θ k. U k represents the set of variables that confound the associations between X k and Y
LLM interpretation
This is a causal directed acyclic graph (DAG) illustrating multivariable Mendelian randomization assumptions. It shows genetic variants ($G_j$) influencing three risk factors ($X_1, X_2, X_3$) via effects $\beta_{Xkj}$, which in turn influence an outcome ($Y$) via causal effects $\theta_k$. The diagram also includes confounding variables ($U_1, U_2, U_3$) affecting the risk factors and outcome, and a dashed line representing a direct pleiotropic effect ($\alpha'_j$) from $G_j$ to $Y$.
Causal directed acyclic graph illustrating the causal relationships between the 2 risk factors X 1 and X 2, and outcome Y. The causal effect of X 1 on X 2 is γ, and the direct causal effect of the risk factor X k on the outcome Y is θ k. The total causal effect of X 1 on Y is θ 1+γ θ 2, consisting of the direct effect (θ 1) and the indirect effect via X 2 (γ θ 2). U k represents the set of variables that confound the associations between X k and Y
LLM interpretation
This figure is a causal directed acyclic graph (DAG) illustrating the relationships between two risk factors ($X_1$, $X_2$) and an outcome ($Y$). Directed arrows indicate a causal path from $X_1$ to $X_2$ (labeled $\gamma$), from $X_1$ to $Y$ (labeled $\theta_1$), and from $X_2$ to $Y$ (labeled $\theta_2$). The diagram visualizes both the direct effect of $X_1$ on $Y$ and an indirect effect mediated through $X_2$.
| Name | Type |
|---|---|
| 185 genetic variants local | variant |
| CARDIoGRAMplusC4D consortium local | cohort |
| CHD | gene |
| CHD risk local | phenotype |
| common variants | cohort |
| confounder U local | phenotype |
| consortia | cohort |
| coronary heart disease | phenotype |
| Friedewald equation local | drug |
| G1 local | variant |
| genetic variants | cohort |
| genomics local | drug |
| G_j local | variant |
| Global Lipids Genetics Consortium local | cohort |
| HDL-C local | drug |
| HDL cholesterol | phenotype |
| high-throughput phenotyping local | drug |
| LDL-C local | drug |
| LDL cholesterol | phenotype |
| lipid fractions local | drug |
| lipid fractions local | phenotype |
| major allele local | variant |
| metabolomics | drug |
| minor allele | variant |
| MR-Egger intercept local | phenotype |
| multiple related phenotypes local | phenotype |
| multivariable MR local | drug |
| multivariable MR-Egger local | drug |
| non-HDL-C local | phenotype |
| outcome | phenotype |
| outcome Y local | phenotype |
| phenotype | phenotype |
| plasma urate concentrations local | phenotype |
| pleiotropic genetic variant local | variant |
| proteomics local | drug |
| reference allele | variant |
| risk factor | phenotype |
| Risk factor 1 local | phenotype |
| Risk Factor 1 local | phenotype |
| Risk factor 2 local | phenotype |
| Risk factor 3 local | phenotype |
| risk factor X local | phenotype |
| risk factor X1 local | phenotype |
| risk factor X2 local | phenotype |
| risk factor X3 local | phenotype |
| risk factor Xk local | phenotype |
| theta band | phenotype |
| total cholesterol | phenotype |
| triglycerides | phenotype |
| X local | phenotype |
| X1 local | phenotype |
| X2 local | phenotype |
| XK local | phenotype |
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| Evaluating causal influence of maternal educational attainment on offspring birthweight via observational study and Mendelian randomization analyses. | Zhu Y et al. | — | 2024 | → |
| Evidence of symptom specificity for depression in multiple sclerosis: A two sample Mendelian randomization study. | Hu C et al. | — | 2024 | → |
| Exploring autism spectrum disorder and co-occurring trait associations to elucidate multivariate genetic mechanisms and insights. | Salenius K et al. | — | 2024 | → |
| Exploring the causal relationship between airborne particulate matter and ulcerative colitis: A two-sample mendelian randomization study. | Fu C et al. | — | 2024 | → |
| Exploring the causal relationship between gut microbiota and atopic dermatitis: A Mendelian randomization study. | Li W et al. | — | 2024 | → |
| Exploring the contribution of lifestyle to the impact of education on the risk of cancer through Mendelian randomization analysis. | Zagkos L et al. | — | 2024 | → |
| Genetic analyses of the bidirectional associations between common mental disorders and asthma. | Yan Z et al. | — | 2024 | → |
| Genetic correlation and causal relationship between sleep and myopia: a mendelian randomization study. | Zhu G et al. | — | 2024 | → |
| Genetic liability of gut microbiota for idiopathic pulmonary fibrosis and lung function: a two-sample Mendelian randomization study. | Ren Y et al. | — | 2024 | → |
| Genetic predisposition to type 2 diabetes mellitus and aortic dissection: a Mendelian randomisation study. | Sun Y et al. | — | 2024 | → |
| Gut Microbiome and Atherosclerosis: A Mendelian Randomization Study. | Li Y et al. | — | 2024 | → |
| Gut microbiota and postpartum depression: a Mendelian randomization study. | Zhang J et al. | — | 2024 | → |
| Insulin-related traits and prostate cancer: A Mendelian randomization study. | Chen G et al. | — | 2024 | → |
| Investigating Causal Effects of Hematologic Traits on Lung Cancer: A Mendelian Randomization Study. | Yang Z et al. | — | 2024 | → |
| Investigating the causal association between systemic lupus erythematosus and migraine using Mendelian randomization analysis. | Xu D et al. | — | 2024 | → |
| Investigating the causal role of the gut microbiota in esophageal cancer and its subtypes: a two-sample Mendelian randomization study. | Li J et al. | — | 2024 | → |
| Lifestyle factors, glycemic traits, and lipoprotein traits and risk of liver cancer: a Mendelian randomization analysis. | Zhang H et al. | — | 2024 | → |
| Major Psychiatric Disorders, Substance Use Behaviors, and Longevity. | Rosoff DB et al. | — | 2024 | → |
| Mammographic density mediates the protective effect of early-life body size on breast cancer risk. | Vabistsevits M et al. | — | 2024 | → |
| Mediating pathways between attention deficit hyperactivity disorder and type 2 diabetes mellitus: evidence from a two-step and multivariable Mendelian randomization study. | Zhang J et al. | — | 2024 | → |
| Mendelian randomization analysis reveals higher whole body water mass may increase risk of bacterial infections. | Yan P et al. | — | 2024 | → |
| MRBEE: A bias-corrected multivariable Mendelian randomization method. | Lorincz-Comi N et al. | — | 2024 | → |
| MRSL: a causal network pruning algorithm based on GWAS summary data. | Hou L et al. | — | 2024 | → |
| MVMRmode: Introducing an R package for plurality valid estimators for multivariable Mendelian randomisation. | Woolf B et al. | — | 2024 | → |
| Nonlinear relationship between high-density lipoprotein cholesterol and cardiovascular disease: an observational and Mendelian randomization analysis. | Chen JX et al. | — | 2024 | → |
| Potential Causal Association Between Atrial Fibrillation/Flutter and Primary Open-Angle Glaucoma: A Two-Sample Mendelian Randomisation Study. | Lee Y et al. | — | 2024 | → |
| Role of blood lipids in mediating the effect of dietary factors on gastroesophageal reflux disease: a two-step mendelian randomization study. | Liu X et al. | — | 2024 | → |
| Sex-specific causality of MRI-derived body compositions on glycaemic traits: Mendelian randomization and observational study. | Zhu Y et al. | — | 2024 | → |
| Shared genetic architecture and causal relationship between sleep behaviors and lifespan. | Wu Y et al. | — | 2024 | → |
| Smoking and alcohol by HPV status in head and neck cancer: a Mendelian randomization study. | Thakral A et al. | — | 2024 | → |
| The association between fruit and vegetable intake and gastrointestinal cancers risk from Mendelian randomization analysis. | Wei J et al. | — | 2024 | → |
| The causal association between type 2 diabetes and spinal stenosis: A Mendelian randomization analysis. | Fan Z et al. | — | 2024 | → |
| The causality between systemic inflammatory regulators and chronic respiratory diseases: A bidirectional Mendelian-randomization study. | Jiang G et al. | — | 2024 | → |
| The causal relationship between blood cell indices and 28-day mortality in sepsis: a retrospective study and bidirectional Mendelian randomization analysis. | Zeng T et al. | — | 2024 | → |
| The Impact of Testosterone on Alzheimer's Disease Are Mediated by Lipid Metabolism and Obesity: A Mendelian Randomization Study. | Zhang L et al. | — | 2024 | → |
| The plasma lipids with different fatty acid chains are associated with the risk of hemorrhagic stroke: a Mendelian randomization study. | Zhang X et al. | — | 2024 | → |
| The Potential Causal Association of Apolipoprotein A and B and Age-Related Macular Degeneration: A Mendelian Randomisation Study. | Lee Y et al. | — | 2024 | → |
| Unveiling therapeutic targets for spinal stenosis from genetic insights: a Mendelian randomization analysis. | Fan Z et al. | — | 2024 | → |
| Adipokines and risk of rheumatoid arthritis: A two-sample multivariable Mendelian randomisation study. | Vasileiadis GK et al. | — | 2023 | → |
| An augmented Mendelian randomization approach provides causality of brain imaging features on complex traits in a single biobank-scale dataset. | Yang A et al. | — | 2023 | → |
| A network causal relationship between type-1 diabetes mellitus, 25-hydroxyvitamin D level and systemic lupus erythematosus: Mendelian randomization study. | Su K et al. | — | 2023 | → |
| Aspirin Use and Risk of Alzheimer's Disease: A 2-Sample Mendelian Randomization Study. | Ding P et al. | — | 2023 | → |
| Association of autoimmune diseases with the occurrence and 28-day mortality of sepsis: an observational and Mendelian randomization study. | Li H et al. | — | 2023 | → |
| Association of Barrett's esophagus with obstructive sleep apnea syndrome: a bidirectional analysis of Mendelian randomization. | Tan W et al. | — | 2023 | → |
| Association of educational attainment with esophageal cancer, Barrett's esophagus, and gastroesophageal reflux disease, and the mediating role of modifiable risk factors: A Mendelian randomization study. | Zhang X et al. | — | 2023 | → |
| Association of regular glucosamine use with incident dementia: evidence from a longitudinal cohort and Mendelian randomization study. | Zheng J et al. | — | 2023 | → |
| Causal association of rheumatoid arthritis with obstructive lung disease: Evidence from Mendelian randomization study. | Cao Z et al. | — | 2023 | → |
| Causal associations between dried fruit intake and cardiovascular disease: A Mendelian randomization study. | Zeng Y et al. | — | 2023 | → |
| Causal associations of obstructive sleep apnea with cardiovascular disease: a Mendelian randomization study. | Li Y et al. | — | 2023 | → |
| Causal inference between rheumatoid arthritis and prostate cancer. | Ou J et al. | — | 2023 | → |
| Causality of occupational exposure on rheumatoid arthritis and ankylosing spondylitis: a two-sample mendelian randomization study. | Du K et al. | — | 2023 | → |
| Causal relationship between gastro-esophageal reflux disease and risk of lung cancer: insights from multivariable Mendelian randomization and mediation analysis. | Liu Y et al. | — | 2023 | → |
| Childhood sunburn and risk of melanoma and non-melanoma skin cancer: a Mendelian randomization study. | Li Y et al. | — | 2023 | → |
| Chronic inflammation does not mediate the effect of adiposity on grip strength: results from a multivariable Mendelian randomization study. | Norris T et al. | — | 2023 | → |
| COVID-19 and cognitive performance: a Mendelian randomization study. | Tang CM et al. | — | 2023 | → |
| Evaluating the causality between skin tanning, radiated disorders, and basal cell carcinoma: a multivariable Mendelian randomization analysis. | Chen C et al. | — | 2023 | → |
| Genetic analyses implicate complex links between adult testosterone levels and health and disease. | Leinonen JT et al. | — | 2023 | → |
| Genetic association and causal inference between lung function and venous thromboembolism. | Zhang Q et al. | — | 2023 | → |
| Genetic insights into resting heart rate and its role in cardiovascular disease. | van de Vegte YJ et al. | — | 2023 | → |
| Genetic support of the causal association between gut microbiome and COVID-19: a bidirectional Mendelian randomization study. | Li Z et al. | — | 2023 | → |
| Gut microbiota and hypertensive disorders in pregnancy: evidence from the Mendelian randomization study. | Wu X et al. | — | 2023 | → |
| Identifying the mediating role of socioeconomic status on the relationship between schizophrenia and major depressive disorder: a Mendelian randomisation analysis. | Xu Q et al. | — | 2023 | → |
| Investigating causal associations among gut microbiota, gut microbiota-derived metabolites, and gestational diabetes mellitus: a bidirectional Mendelian randomization study. | Wu X et al. | — | 2023 | → |
| Longitudinal change of gut microbiota in hypertensive disorders in pregnancy: a nested case-control and Mendelian randomization study. | Wu X et al. | — | 2023 | → |
| Mendelian randomization analyses support causal relationship between gut microbiota and childhood obesity. | Li Q et al. | — | 2023 | → |
| Mendelian randomization analysis suggests no causal influence of gastroesophageal reflux disease on the susceptibility and prognosis of idiopathic pulmonary fibrosis. | Sun D et al. | — | 2023 | → |
| Multi-response Mendelian randomization: Identification of shared and distinct exposures for multimorbidity and multiple related disease outcomes. | Zuber V et al. | — | 2023 | → |
| New proposal to address mediation analysis interrogations by using genetic variants as instrumental variables. | Coscia C et al. | — | 2023 | → |
| Robust multivariable Mendelian randomization based on constrained maximum likelihood. | Lin Z et al. | — | 2023 | → |
| Roles of gut microbiome in epilepsy risk: A Mendelian randomization study. | Zeng Y et al. | — | 2023 | → |
| Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study. | Papadimitriou N et al. | — | 2023 | → |
| The causal role of gastroesophageal reflux disease in anxiety disorders and depression: A bidirectional Mendelian randomization study. | Zeng Y et al. | — | 2023 | → |
| The relationship between gut microbiota and insomnia: a bi-directional two-sample Mendelian randomization research. | Li Y et al. | — | 2023 | → |
| The role of plasma cortisol in dementia, epilepsy, and multiple sclerosis: A Mendelian randomization study. | Li H et al. | — | 2023 | → |
| Unlocking the Medicinal Mysteries: Preventing Lacunar Stroke with Drug Repurposing. | Zhang L et al. | — | 2023 | → |
| A Mendelian randomization study of the effect of tea intake on breast cancer. | Deng Y et al. | — | 2022 | → |
| An efficient and robust approach to Mendelian randomization with measured pleiotropic effects in a high-dimensional setting. | Grant AJ et al. | — | 2022 | → |
| A practical problem with Egger regression in Mendelian randomization. | Lin Z et al. | — | 2022 | → |
| Association between Microbiome-Related Human Genetic Variants and Fasting Plasma Glucose in a High-Cardiovascular-Risk Mediterranean Population. | Asensio EM et al. | — | 2022 | → |
| Association of smoking, lung function and COPD in COVID-19 risk: a two-step Mendelian randomization study. | Au Yeung SL et al. | — | 2022 | → |
| Associations of Lipids and Lipid-Lowering Drugs with Risk of Vascular Dementia: A Mendelian Randomization Study. | Zhang X et al. | — | 2022 | → |
| Bidirectional two-sample Mendelian randomization analysis identifies causal associations between relative carbohydrate intake and depression. | Yao S et al. | — | 2022 | → |
| Causal effects of systemic lupus erythematosus on endometrial cancer: A univariable and multivariable Mendelian randomization study. | Wan A et al. | — | 2022 | → |
| Causal mediation analysis with multiple causally non-ordered and ordered mediators based on summarized genetic data. | Hou L et al. | — | 2022 | → |
| Causal relationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study. | Wang YB et al. | — | 2022 | → |
| Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach. | Richardson TG et al. | — | 2022 | → |
| Cigarette Smoking and Endometrial Cancer Risk: Observational and Mendelian Randomization Analyses. | Dimou N et al. | — | 2022 | → |
| Circulating vitamin C and D concentrations and risk of dental caries and periodontitis: A Mendelian randomization study. | Hu Z et al. | — | 2022 | → |
| Deciphering how early life adiposity influences breast cancer risk using Mendelian randomization. | Vabistsevits M et al. | — | 2022 | → |
| Dehydroepiandrosterone Sulfate and Colorectal Cancer Risk: A Mendelian Randomization Analysis. | Jayarathna DK et al. | — | 2022 | → |
| Estimation of causal effects of a time-varying exposure at multiple time points through multivariable mendelian randomization. | Sanderson E et al. | — | 2022 | → |
| Evaluation of bi-directional causal association between depression and cardiovascular diseases: a Mendelian randomization study. | Li GH et al. | — | 2022 | → |
| Genetic estimation of correlations and causalities between multifaceted modifiable factors and gastro-oesophageal reflux disease. | Sun Y et al. | — | 2022 | → |
| HDL cholesterol concentrations and risk of atherosclerotic cardiovascular disease - Insights from randomized clinical trials and human genetics. | Kjeldsen EW et al. | — | 2022 | → |
| Impact of Cortisol on Reduction in Muscle Strength and Mass: A Mendelian Randomization Study. | Katsuhara S et al. | — | 2022 | → |
| Impact of lung function on cardiovascular diseases and cardiovascular risk factors: a two sample bidirectional Mendelian randomisation study. | Au Yeung SL et al. | — | 2022 | → |
| Influences on the Genetic Relationship Between Cannabis Use and Schizophrenia: The Role of the Externalizing Spectrum. | Wormington B et al. | — | 2022 | → |
| Integrating multi-omics summary data using a Mendelian randomization framework. | Jin C et al. | — | 2022 | → |
| Investigating the Association Between Seven Sleep Traits and Nonalcoholic Fatty Liver Disease: Observational and Mendelian Randomization Study. | Fan H et al. | — | 2022 | → |
| Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization. | Gormley M et al. | — | 2022 | → |
| Lipids, Apolipoproteins, Statins, and Intracerebral Hemorrhage: A Mendelian Randomization Study. | Yu Z et al. | — | 2022 | → |
| Mendelian randomization prioritizes abdominal adiposity as an independent causal factor for liver fat accumulation and cardiometabolic diseases. | Gagnon E et al. | — | 2022 | → |
| Metabolic and lifestyle factors in relation to senile cataract: a Mendelian randomization study. | Yuan S et al. | — | 2022 | → |
| The causal association of polyunsaturated fatty acids with allergic disease: A two-sample Mendelian randomization study. | Li Y et al. | — | 2022 | → |
| The causes and consequences of Alzheimer's disease: phenome-wide evidence from Mendelian randomization. | Korologou-Linden R et al. | — | 2022 | → |
| The relationship between lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation study. | Ioannidou A et al. | — | 2022 | → |
| Thyroid Stimulating Hormone Levels Are Associated With Genetically Predicted Nonalcoholic Fatty Liver Disease. | Fan H et al. | — | 2022 | → |
| Type 2 diabetes mellitus increases risk of erectile dysfunction independent of obesity and dyslipidemia: A Mendelian randomization study. | Yuan C et al. | — | 2022 | → |
| Understanding the assumptions underlying Mendelian randomization. | de Leeuw C et al. | — | 2022 | → |
| A Hierarchical Approach Using Marginal Summary Statistics for Multiple Intermediates in a Mendelian Randomization or Transcriptome Analysis. | Jiang L et al. | — | 2021 | → |
| A life course approach to elucidate the role of adiposity in asthma risk: evidence from a Mendelian randomisation study. | Au Yeung SL et al. | — | 2021 | → |
| Assessing the Causal Relationships Between Insulin Resistance and Hyperuricemia and Gout Using Bidirectional Mendelian Randomization. | McCormick N et al. | — | 2021 | → |
| Assessing the linear and non-linear association of HbA<sub>1c</sub> with cardiovascular disease: a Mendelian randomisation study. | Luo S et al. | — | 2021 | → |
| Assessment and visualization of phenome-wide causal relationships using genetic data: an application to dental caries and periodontitis. | Haworth S et al. | — | 2021 | → |
| Associations of Arachidonic Acid Synthesis with Cardiovascular Risk Factors and Relation to Ischemic Heart Disease and Stroke: A Univariable and Multivariable Mendelian Randomization Study. | Zhang T et al. | — | 2021 | → |
| Atrial fibrillation and left atrial size and function: a Mendelian randomization study. | van de Vegte YJ et al. | — | 2021 | → |
| Causal effect of sex hormone-binding globulin and testosterone on coronary heart disease: A multivariable and network Mendelian randomization analysis. | Li Y et al. | — | 2021 | → |
| Causal effects of atrial fibrillation on brain white and gray matter volume: a Mendelian randomization study. | Park S et al. | — | 2021 | → |
| Causal Relationship Between Lung Function and Atrial Fibrillation: A Two Sample Univariable and Multivariable, Bidirectional Mendelian Randomization Study. | Zhang Q et al. | — | 2021 | → |
| Causal relationships between blood lipids and depression phenotypes: a Mendelian randomisation analysis. | So HC et al. | — | 2021 | → |
| Causal relationships between body mass index, smoking and lung cancer: Univariable and multivariable Mendelian randomization. | Zhou W et al. | — | 2021 | → |
| Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses. | Molina-Montes E et al. | — | 2021 | → |
| Discordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy. | Verhoef E et al. | — | 2021 | → |
| Effect of Basal Metabolic Rate on Cancer: A Mendelian Randomization Study. | Ng JCM et al. | — | 2021 | → |
| Effects of apolipoprotein B on lifespan and risks of major diseases including type 2 diabetes: a mendelian randomisation analysis using outcomes in first-degree relatives. | Richardson TG et al. | — | 2021 | → |
| Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus. | Tin A et al. | — | 2021 | → |
| Evaluating the direct effects of childhood adiposity on adult systemic metabolism: a multivariable Mendelian randomization analysis. | Richardson TG et al. | — | 2021 | → |
| Extension of Mendelian Randomization to Identify Earliest Manifestations of Alzheimer Disease: Association of Genetic Risk Score for Alzheimer Disease With Lower Body Mass Index by Age 50 Years. | Brenowitz WD et al. | — | 2021 | → |
| Genetically Determined TSH Level Within Reference Range Is Inversely Associated With Alzheimer Disease. | Li GH et al. | — | 2021 | → |
| Genetically predicted education attainment in relation to somatic and mental health. | Yuan S et al. | — | 2021 | → |
| Genetically predicted sex hormone binding globulin and ischemic heart disease in men and women: a univariable and multivariable Mendelian randomization study. | Zhao JV et al. | — | 2021 | → |
| Investigating Effects of Plasma Apolipoprotein E on Ischemic Heart Disease Using Mendelian Randomization Study. | Li MY et al. | — | 2021 | → |
| Investigating the causal effect of fibroblast growth factor 23 on osteoporosis and cardiometabolic disorders: A Mendelian randomization study. | Yokomoto-Umakoshi M et al. | — | 2021 | → |
| Lipid and metabolic syndrome traits in coronary artery disease: a Mendelian randomization study. | Thomas DG et al. | — | 2021 | → |
| Mendelian randomisation for mediation analysis: current methods and challenges for implementation. | Carter AR et al. | — | 2021 | → |
| Multivariable Mendelian Randomization and Mediation. | Sanderson E | — | 2021 | → |
| Pleiotropy robust methods for multivariable Mendelian randomization. | Grant AJ et al. | — | 2021 | → |
| Sex-specific Associations of Sex Hormone Binding Globulin with CKD and Kidney Function: A Univariable and Multivariable Mendelian Randomization Study in the UK Biobank. | Zhao JV et al. | — | 2021 | → |
| Smoking is significantly associated with increased risk of COVID-19 and other respiratory infections. | Rosoff DB et al. | — | 2021 | → |
| Testing and correcting for weak and pleiotropic instruments in two-sample multivariable Mendelian randomization. | Sanderson E et al. | — | 2021 | → |
| The causal effects of serum lipids and apolipoproteins on kidney function: multivariable and bidirectional Mendelian-randomization analyses. | Rasheed H et al. | — | 2021 | → |
| The effects of eight serum lipid biomarkers on age-related macular degeneration risk: a Mendelian randomization study. | Han X et al. | — | 2021 | → |
| The relationship between cannabis and schizophrenia: a genetically informed perspective. | Johnson EC et al. | — | 2021 | → |
| The total and direct effects of systolic and diastolic blood pressure on cardiovascular disease and longevity using Mendelian randomisation. | Chan II et al. | — | 2021 | → |
| Two-Sample Multivariable Mendelian Randomization Analysis Using R. | Rasooly D et al. | — | 2021 | → |
| Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics. | Gordillo-Marañón M et al. | — | 2021 | → |
| A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer. | Gormley M et al. | — | 2020 | → |
| Association of genetic risk for Alzheimer disease and hearing impairment. | Brenowitz WD et al. | — | 2020 | → |
| Causal Effects of Overall and Abdominal Obesity on Insulin Resistance and the Risk of Type 2 Diabetes Mellitus: A Two-Sample Mendelian Randomization Study. | Xu H et al. | — | 2020 | → |
| Comprehensive Investigation of Circulating Biomarkers and Their Causal Role in Atherosclerosis-Related Risk Factors and Clinical Events. | Zanetti D et al. | — | 2020 | → |
| Desaturase Activity and the Risk of Type 2 Diabetes and Coronary Artery Disease: A Mendelian Randomization Study. | Jäger S et al. | — | 2020 | → |
| Educational attainment reduces the risk of suicide attempt among individuals with and without psychiatric disorders independent of cognition: a bidirectional and multivariable Mendelian randomization study with more than 815,000 participants. | Rosoff DB et al. | — | 2020 | → |
| Education, intelligence and Alzheimer's disease: evidence from a multivariable two-sample Mendelian randomization study. | Anderson EL et al. | — | 2020 | → |
| Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study. | Rosoff DB et al. | — | 2020 | → |
| Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis. | Richardson TG et al. | — | 2020 | → |
| Evaluation of causality between ADHD and Parkinson's disease: Mendelian randomization study. | Li GH et al. | — | 2020 | → |
| Implicating causal brain imaging endophenotypes in Alzheimer's disease using multivariable IWAS and GWAS summary data. | Knutson KA et al. | — | 2020 | → |
| Inferring causal direction between two traits in the presence of horizontal pleiotropy with GWAS summary data. | Xue H et al. | — | 2020 | → |
| Inferring Causal Direction Between Two Traits in the Presence of Horizontal Pleiotropy with GWAS Summary Data | Xue H et al. | — | 2020 | — |
| Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian randomisation. | Schooling CM et al. | — | 2020 | → |
| Investigating the Causal Effect of Brain Expression of <i>CCL2</i>, <i>NFKB1</i>, <i>MAPK14</i>, <i>TNFRSF1A</i>, <i>CXCL10</i> Genes on Multiple Sclerosis: A Two-Sample Mendelian Randomization Approach. | Fazia T et al. | — | 2020 | → |
| Mendelian randomization and experimental IUGR reveal the adverse effect of low birth weight on lung structure and function. | Kuiper-Makris C et al. | — | 2020 | → |
| MendelianRandomization v0.5.0: updates to an R package for performing Mendelian randomization analyses using summarized data. | Broadbent JR et al. | — | 2020 | → |
| Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci. | Erzurumluoglu AM et al. | — | 2020 | → |
| Selecting likely causal risk factors from high-throughput experiments using multivariable Mendelian randomization. | Zuber V et al. | — | 2020 | → |
| The effect of liver enzymes on body composition: A Mendelian randomization study. | Liu J et al. | — | 2020 | → |
| The role of testosterone in chronic kidney disease and kidney function in men and women: a bi-directional Mendelian randomization study in the UK Biobank. | Zhao JV et al. | — | 2020 | → |
| Understanding the nature of association between anxiety phenotypes and anorexia nervosa: a triangulation approach. | Lloyd EC et al. | — | 2020 | → |
| Urinary Albumin, Sodium, and Potassium and Cardiovascular Outcomes in the UK Biobank: Observational and Mendelian Randomization Analyses. | Zanetti D et al. | — | 2020 | → |
| Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study. | Richardson TG et al. | — | 2020 | → |
| Use of Multivariable Mendelian Randomization to Address Biases Due to Competing Risk Before Recruitment. | Schooling CM et al. | — | 2020 | → |
| An examination of multivariable Mendelian randomization in the single-sample and two-sample summary data settings. | Sanderson E et al. | — | 2019 | → |
| Assessing the Role of Selenium in Endometrial Cancer Risk: A Mendelian Randomization Study. | Kho PF et al. | — | 2019 | → |
| Associations of Smoking and Alcohol and Coffee Intake with Fracture and Bone Mineral Density: A Mendelian Randomization Study. | Yuan S et al. | — | 2019 | → |
| Causal association between rheumatoid arthritis and a decreased risk of Alzheimer's disease : A Mendelian randomization study. | Bae SC et al. | — | 2019 | → |
| Education protects against coronary heart disease and stroke independently of cognitive function: evidence from Mendelian randomization. | Gill D et al. | — | 2019 | → |
| Effect of age at puberty on risk of multiple sclerosis: A mendelian randomization study. | Harroud A et al. | — | 2019 | → |
| Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration. | Wilman HR et al. | — | 2019 | → |
| Genome-wide association meta-analysis and Mendelian randomization analysis confirm the influence of ALDH2 on sleep durationin the Japanese population. | Nishiyama T et al. | — | 2019 | → |
| Guidelines for performing Mendelian randomization investigations: update for summer 2023. | Burgess S et al. | — | 2019 | → |
| Mendelian randomisation analysis of the effect of educational attainment and cognitive ability on smoking behaviour. | Sanderson E et al. | — | 2019 | → |
| Mendelian randomisation and the goal of inferring causation from observational studies in the vision sciences. | Plotnikov D et al. | — | 2019 | → |
| Mendelian randomization in the bone field. | Larsson SC et al. | — | 2019 | → |
| Sex hormone binding globulin and risk of breast cancer: a Mendelian randomization study. | Dimou NL et al. | — | 2019 | → |
| The association between weight at birth and breast cancer risk revisited using Mendelian randomisation. | Kar SP et al. | — | 2019 | → |
| Using a two-sample Mendelian randomization design to investigate a possible causal effect of maternal lipid concentrations on offspring birth weight. | Hwang LD et al. | — | 2019 | → |
| Challenges in Interpreting Multivariable Mendelian Randomization: Might "Good Cholesterol" Be Good After All? | Holmes MV et al. | — | 2018 | → |
| Evaluating the potential role of pleiotropy in Mendelian randomization studies. | Hemani G et al. | — | 2018 | → |
| Inferring Causal Relationships Between Risk Factors and Outcomes from Genome-Wide Association Study Data. | Burgess S et al. | — | 2018 | → |
| Invited Commentary: Detecting Individual and Global Horizontal Pleiotropy in Mendelian Randomization-A Job for the Humble Heterogeneity Statistic? | Bowden J et al. | — | 2018 | → |
| Lung Function and Coronary Artery Disease Risk. | Nowak C | — | 2018 | → |
| Using genetic data to strengthen causal inference in observational research. | Pingault JB et al. | — | 2018 | → |
| Extending the MR-Egger method for multivariable Mendelian randomization to correct for both measured and unmeasured pleiotropy. | Rees JMB et al. | — | 2017 | → |