Cited by 1,215Advanced Causal Inference TechniquesGenetic Associations and EpidemiologyStatistical Methods in Epidemiology

The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.

Mendelian randomisation for mediation analysis: current methods and challenges for implementation

Open access

Carter, Alice R., Sanderson, Eleanor, Hammerton, Gemma, Richmond, Rebecca C., Davey Smith, George, Heron, Jon, Taylor, Amy E., Davies, Neil M., Howe, Laura D.·2021·European Journal of Epidemiology

DOI 10.1007/s10654-021-00757-1PMC PMC8159796

Published version of a preprint

Open this paper in CoChat — free account Open PDF

Abstract

Mediation analysis seeks to explain the pathway(s) through which an exposure affects an outcome. Traditional, non-instrumental variable methods for mediation analysis experience a number of methodological difficulties, including bias due to confounding between an exposure, mediator and outcome and measurement error. Mendelian randomisation (MR) can be used to improve causal inference for mediation analysis. We describe two approaches that can be used for estimating mediation analysis with MR: multivariable MR (MVMR) and two-step MR. We outline the approaches and provide code to demonstrate how they can be used in mediation analysis. We review issues that can affect analyses, including confounding, measurement error, weak instrument bias, interactions between exposures and mediators and analysis of multiple mediators. Description of the methods is supplemented by simulated and real data examples. Although MR relies on large sample sizes and strong assumptions, such as having strong instruments and no horizontally pleiotropic pathways, our simulations demonstrate that these methods are unaffected by confounders of the exposure or mediator and the outcome and non-differential measurement error of the exposure or mediator. Both MVMR and two-step MR can be implemented in both individual-level MR and summary data MR. MR mediation methods require different assumptions to be made, compared with non-instrumental variable mediation methods. Where these assumptions are more plausible, MR can be used to improve causal inference in mediation analysis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1007/s10654-021-00757-1

Cites

70 of 70 references verified0 citation errors · 0 not checkable

Statistics

Fig. 1 The decomposed effects in a non-IV regression-based mediation analysis where c represents the total effect, c' represents the direct effect and the indirect effect can be calculated by subtracting c’ from c (difference method) or multiplying A times B (product of coefficients method) b multivariable Mendelian randomisation, using a combined genetic instrument for both the exposure and mediator of interest, to estimate the direct effect c' of the exposure and c two-step Mendelian randomisation, where the effect of the exposure on the mediator (A) and mediator on the outcome b are estimated separately, using separate genetic instrumental variables for both the exposure and mediator. These estimates are then multiplied together to estimate the indirect effect of the mediator (A*B)CC BY · PubMed Central

Fig. 2 Schematic diagram illustrating the causal assumptions (dashed lines) in a non-IV regression-based mediation methods and b Mendelian randomisation mediation analysis with the measured associations in solid black lines. Additional assumptions: in non-IV mediation there is no measurement error in the exposure or mediator; in Mendelian randomisation mediation there is no exposure-mediator interaction. In Mendelian randomisation, the exclusion restriction criteria mean there are no alternative pathways from the instrument to the outcome other than via the exposure (or mediator) of interestCC BY · PubMed Central

Fig. 3 Size of absolute bias for the indirect effect of an exposure on a continuous outcome, rare binary outcome and common binary outcome through a continuous mediator, for a range of fixed true total effect sizes (0.2, 0.5 and 1.0) and range of true indirect effect sizes using non-IV regression based mediation methods or Mendelian randomisation, on the relative scale (simulated N = 5000). In all scenarios, unmeasured confounding is simulatedCC BY · PubMed Central

Fig. 4 Flow chart for analytical processes when carrying out mediation analyses using individual level Mendelian randomisationCC BY · PubMed Central

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The moderator-mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations
Baron, R. M., & Kenny, D. A. (1986) · Journal of Personality and Social Psychology · doi:10.1037/0022-3514.51.6.1173 · Cited by 91,532
Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression
Bowden, J., Davey Smith, G., & Burgess, S. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv080 · Cited by 9,816
A comparison of methods to test mediation and other intervening variable effects
MacKinnon, D. P., Lockwood, C. M., Hoffman, J. M., West, S. G., & Sheets, V. (2002) · Psychological Methods · doi:10.1037/1082-989x.7.1.83 · Cited by 9,406
Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator
Bowden, J., Davey Smith, G., Haycock, P. C., & Burgess, S. (2016) · Genetic Epidemiology · doi:10.1002/gepi.21965 · Cited by 8,922
Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data
Burgess, S., Butterworth, A., & Thompson, S. G. (2013) · Genetic Epidemiology · doi:10.1002/gepi.21758 · Cited by 6,050
‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?*
Davey Smith, G., & Ebrahim, S. (2003) · International Journal of Epidemiology · doi:10.1093/ije/dyg070 · Cited by 5,882
Mediation Analysis
MacKinnon, D. P., Fairchild, A. J., & Fritz, M. S. (2007) · Annual Review of Psychology · doi:10.1146/annurev.psych.58.110405.085542 · Cited by 5,688
Mendelian randomization: genetic anchors for causal inference in epidemiological studies
Davey Smith, G., & Hemani, G. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu328 · Cited by 4,677
Mendelian randomization: Using genes as instruments for making causal inferences in epidemiology
Lawlor, D. A., Harbord, R. M., Sterne, J. A. C., Timpson, N., & Davey Smith, G. (2008) · Statistics in Medicine · doi:10.1002/sim.3034 · Cited by 4,618
Genetic studies of body mass index yield new insights for obesity biology
Study, T. L. C., Locke, A. E., The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The, G. L. G. C., The, I. C. B. P., The MAGIC Investigators, The MuTHER Consortium, et al. (2015) · Nature · doi:10.1038/nature14177 · Cited by 4,534

Show all 67 references

Research works printed but not linked: 1

Richardson TG, Sanderson E, Elsworth B, Tilling K, Davey SG. Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study. BMJ. 2020;369:m1203. https://doi.org/10.1136/bmj.m1203. · DOI · Paper page

Sorted by citations

Items 801–900 of 1,001

Combination of QTL and GWAS to uncover the role of phosphodiesterases in ischemic heart diseasePreprint
Xiao, J., Gao, Z., Wei, H., Wei, Y., Qiu, Z., & Huang, W. (2023) · medRxiv · doi:10.1101/2023.09.24.23296052
Causal Relationship between Number of Live Births and Breast Cancer: Two Sample Mendelian Randomisation Analysis
邵, 馨. (2023) · Advances in Clinical Medicine · doi:10.12677/acm.2023.13102137
Associations of Education with Cholelithiasis and the Mediating Effects of Cardiometabolic Factors: A Mendelian Randomization StudyPreprint
Li, C., Liu, Y., Lan, Y., & Wang, Z. (2023) · Research Square · doi:10.21203/rs.3.rs-3552461/v1
Membranous Nephropathy: Muti-omics Mendelian randomization and colocalization analysisPreprint
Su, Z., Liu, W., Yin, Z., Wu, D., Cheng, Y. S., & Wan, Q. (2023) · medRxiv · doi:10.1101/2023.11.21.23298831
Causal Relationship Between Liver Iron Content, Liver Fat Percentage, Liver Volume, and Hepatocellular Carcinoma: A Mendelian Randomization StudyPreprint
Han, T., Li, C., Wang, B., Xu, Y., & Xu, B. (2023) · Research Square · doi:10.21203/rs.3.rs-3649517/v1
Mendelian randomization analysis identifies a causal effect of Streptococcus salivarius on DR mediating via the level of host fasting glucosePreprint
Li, J., Zheng, G., Jiang, D., Deng, C., Zhang, Y., Ma, Y., & Su, J. (2023) · medRxiv · doi:10.1101/2023.12.19.23300249
Mendelian randomization reveals pleiotropic genes between major depression and bowel cancerPreprint
Xiao, C., Shen, J., Yan, H., Zhang, H., & Ye, L. (2023) · Research Square · doi:10.21203/rs.3.rs-3772075/v1
Periodontal health status and its association with cardiovascular risk score among the rural community in India: A community-based study
Radhakrishnan, S., & Saravanan, N. (2023) · MGM Journal of Medical Sciences · doi:10.4103/mgmj.mgmj_17_23
Causal association of gut microbiota with type 2 diabetes, type 1 diabetes and glycemic traits: a two-sample Mendelian randomization studyPreprint
Zhao, J., Xing, W., Li, Y., Mao, Z., Wang, C., Zhang, S., Li, Z., Li, Y., Li, J., Yang, T., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-3865977/v1
Commentary: Causal associations of gut microbiota and metabolites on sepsis: a two-sample Mendelian randomization study
Xu, J., & Zhang, H. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1339176
Cholesterol and Vitamin D and the Risk of Hyperemesis Gravidarum: A Mendelian Randomization StudyPreprint
Liu, X., Zhou, X., Wang, J., Cai, A., Zhang, Y., Zhang, J., Wu, Z., & Zhu, B. (2024) · Research Square · doi:10.21203/rs.3.rs-3897391/v1
Causal effects of endometriosis on cancer risk: A Mendelian randomization study
Tang, T., Yu, H., Xu, S., Zhong, Y., Ma, J., & Zhao, T. (2024) · International Journal of Cancer · doi:10.1002/ijc.34876
Genetically predicted Vascular endothelial growth factor A mediates the association between CD3+ CD8+ TD T cell and Colorectal cancer: A Mendelian randomization analysisPreprint
Zhang, Q., Chen, B., Zhou, X., Cheng, S., Hou, D., Wu, X.-J., Zhang, D., & Zhu, S. (2024) · Research Square · doi:10.21203/rs.3.rs-3963144/v1
Connecting atrial fibrillation to digestive neoplasms: exploring mediation via ischemic stroke and heart failure in Mendelian randomization studies
Xu, Z., Rao, X., Xing, Y., Zhu, Z., Yan, L., Huang, J. V., Zhang, J., & Zheng, R. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1301327
Causal relationship between prostate cancer and cardiovascular diseases: Univariable and multivariable Mendelian randomizationPreprint
wu, X., Zhang, W., Chen, H., & Weng, J. (2024) · Research Square · doi:10.21203/rs.3.rs-3757050/v1
Causal relationships between systolic blood pressure and ischemic stroke based on two-sample Mendelian randomizationPreprint
Liu, X.-H., Yang, Z.-H., Zhou, Y., Luo, J.-Z., & Yao, R.-L. (2024) · Research Square · doi:10.21203/rs.3.rs-3971380/v1
Evidence of the relationship between periodontal diseases/caries and cardiovascular diseases: a systematic review
de Freitas, I. R., Crepaldi, A. J. B., Basta, J., & Scriboni, A. B. (2024) · MedNEXT Journal of Medical and Health Sciences · doi:10.54448/mdnt24s104
A protective causal relationship between morphine and colorectal cancer: a two-way Mendelian randomization studyPreprint
Deng, Q., Yu, Y., Yu, C., Luo, H., Gong, C., & Wang, X. W. (2024) · Research Square · doi:10.21203/rs.3.rs-4007465/v1
Systematic exploration of the causal relationships among gallstones, cholecystectomy, and 33 types of site-specific cancers: A Mendelian randomization study based on after-meta analysisPreprint
Teng, F., Tang, Y., Lu, Z., & Chen, Z. (2024) · Research Square · doi:10.21203/rs.3.rs-4019290/v1
The Mediating Effect of 3-Methoxytyrosine on TWEAK Levels and Primary Sclerosing Cholangitis: A Genetic PerspectivePreprint
Zhou, J., Xun, Y., & Liu, Z. (2024) · Research Square · doi:10.21203/rs.3.rs-3993883/v1
Educational Attainment and Supraventricular Tachycardia: A Mendelian Randomization StudyPreprint
Xu, R., Zhong, Z., & Chen, Q. (2024) · Research Square · doi:10.21203/rs.3.rs-4084844/v1
Mendelian Randomization Investigation: Exploring the Relationship Between Sphingomyelin levels and Hypertrophic Cardiomyopathy Risk through Interleukin-10 levelsExpressionPreprint
shi, J., & li, H. (2024) · Research Square · doi:10.21203/rs.3.rs-4005452/v1
Association of birth weight, childhood obesity, and age at menarche with ovarian function: an integrated Mendelian randomization study and bioinformatics analysisPreprint
Dang, C., Liu, P., Liu, J., & Yu, X. (2024) · Research Square · doi:10.21203/rs.3.rs-4119845/v1
Additional file 1 of Modifiable risk factors that mediate the effect of educational attainment on the risk of stroke: a network Mendelian randomization study
Wan, B., Ma, N., Zhou, Z., & Lu, W. (2023) · Figshare · doi:10.6084/m9.figshare.22807425
Additional file 1 of The hepato-ovarian axis: genetic evidence for a causal association between non-alcoholic fatty liver disease and polycystic ovary syndrome
Liu, D., Gao, X., Pan, X., Zhou, T., Zhu, C., Li, F. R., Fan, J., Targher, G., & Zhao, J. (2023) · Figshare · doi:10.6084/m9.figshare.22610861
Additional file 2 of Modifiable risk factors that mediate the effect of educational attainment on the risk of stroke: a network Mendelian randomization study
Wan, B., Ma, N., Zhou, Z., & Lu, W. (2023) · Figshare · doi:10.6084/m9.figshare.22807428
Additional file 6 of Lifestyle factors, metabolic factors and socioeconomic status for pelvic organ prolapse: a Mendelian randomization study
Liu, H., Wu, W., Xiang, W., & Yuan, J. (2023) · Figshare · doi:10.6084/m9.figshare.23354491
Additional file 5 of Lifestyle factors, metabolic factors and socioeconomic status for pelvic organ prolapse: a Mendelian randomization study
Liu, H., Wu, W., Wei, X., & Yuan, J. (2023) · Figshare · doi:10.6084/m9.figshare.23354488
A commentary on ‘Complex causal association between genetically predicted 731 immunocyte phenotype and osteonecrosis: a bidirectional two-sample Mendelian randomization analysis’
Lin, Y., Zhao, R., & Yang, Q. (2024) · International Journal of Surgery · doi:10.1097/js9.0000000000001436
Circulating Inflammatory Biomarkers mediates the causal effect of Aging on Female Pelvic Organ Prolapse: Mendelian Randomization AnalysisPreprint
Huang, X., Xiao, Y., Chen, M., Zhu, F., Chen, L., Tian, X., & Hong, L. (2024) · Research Square · doi:10.21203/rs.3.rs-4138072/v1
Understanding the Causal Relationships Between Opioid Dependence and Risk of Mental Disorders: A Comprehensive Two-Sample Mendelian Randomization Study
Hu, Y., Qian, L., Shi, R., Duan, H., & Lin, X. (2024) · International Journal of Mental Health and Addiction · doi:10.1007/s11469-024-01315-y
Obesity and hypertension mediate the effect of education on deep intracerebral hemorrhage: A Mendelian randomization study
Sun, H., Zhong, Y., Liao, L., Wu, J., Xu, H., & Ma, J. (2024) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2024.107758 · Cited by 1
Mediation Effect of Plasma Metabolites on the Relationship between Immune Cells and the Risk of Prostatitis: A Study by Bidirectional Two-Sample and Bayesian-Weighted Mendelian RandomizationPreprint
Ding, C., Gong, Q., & Wan, S. (2024) · Research Square · doi:10.21203/rs.3.rs-4345622/v1
Dietary preference and susceptibility to type 2 diabetes mellitus: a wide-angle Mendelian randomization studyPreprint
Lee, D., & Voight, B. F. (2024) · medRxiv · doi:10.1101/2024.05.05.24306877
Air Pollution as a Risk Factor Affecting Human Health and Economic Costs
(2024) · Frontiers research topics · doi:10.3389/978-2-8325-4914-8
Evidence for a Causal Link between Early Liver Disease and Cataracts: A Prospective Study and Mendelian Randomization AnalysisPreprint
Yang, L., Shen, Q., Huang, H., Xie, J., Liu, Z., & Xu, C. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4850050
Effect of smoking on prostate cancer: Results from the National Health and Nutrition Examination Survey 2003–2018 and Mendelian randomization analyses
He, H., Liang, L., Tian, T., Zhang, X., & Lyu, J. (2024) · Tobacco Induced Diseases · doi:10.18332/tid/189199
Causal effects of AP on ovarian cancer risk in European and East Asian populations: a Mendelian randomization studyPreprint
Tong, Y., lai, Z., & Liu, Z. (2024) · Research Square · doi:10.21203/rs.3.rs-4368592/v1
Genetically Informed Study Highlights Income-Independent Effect of Schizophrenia Liability on Mental and Physical Health
Kouakou, M. R., Cabrera‐Mendoza, B., Pathak, G. A., Cannon, T. D., & Polimanti, R. A. (2024) · Schizophrenia Bulletin · doi:10.1093/schbul/sbae093
Blood metabolites mediate the causal relationship between circulating CX3CL1 levels and prostate cancer: A 2-step Mendelian randomization study
Zhou, Y., Chen, Z., Guo, Z., Gao, G., Duan, Y., Wang, H., Sun, L., Huang, W., & Zhuo, Y. (2024) · Medicine · doi:10.1097/md.0000000000038433
Genetic association of lipids and lipid-lowering drug targets with the risk of type 1 diabetes and its complicationsPreprint
Wang, H., Liu, Z., Yang, Z., Lu, Y., & Zou, C. (2024) · Research Square · doi:10.21203/rs.3.rs-4537908/v1
Causal relationship between immune cells and osteoarthritis: a two-sample Mendelian randomization studyPreprint
Tan, G.-C., Yang, J., Tang, Q., & Liu, H. (2024) · Research Square · doi:10.21203/rs.3.rs-4534825/v1
Type 2 diabetes, glycaemic traits, structural brain capacity and cognitive function: A Mendelian randomization analysis
Luo, M., Sun, M., Wang, T., Wei, J., Ruan, X., Chen, K., Ou, J., Chen, Y., & Qin, J. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15702 · Cited by 1
The association between an unhealthy lifestyle and osteomyelitis is mediated by immune cells: A Mendelian randomization studyPreprint
Yang, X., Kadier, X., Xiong, D., Wang, S., & Yusufu, A. (2024) · Research Square · doi:10.21203/rs.3.rs-4525230/v1
Association of education with cholelithiasis and mediating effects of cardiometabolic factors: A Mendelian randomization study
Li, C., Liu, Y.-K., Lan, Y., & Wang, Z. (2024) · World Journal of Clinical Cases · doi:10.12998/wjcc.v12.i20.4272
The Mediating Role of IDL Particles in the Relationship between Primary Hypertension and Cardiovascular Diseases: Insights from Mendelian Randomization and Multi-Omics AnalysisPreprint
Liu, Y., Wu, H., Lv, H., & Zhou, Y. (2024) · Research Square · doi:10.21203/rs.3.rs-4588496/v1
Effect of Relative Protein Intake on Hypertension and Mediating Role of Physical Fitness and Circulating Fatty Acids
Ye, C., Liu, D., Kong, L., Wang, Y., Dou, C., Xu, M., Zheng, R., Zheng, R., Li, M., Zhao, Z., et al. (2024) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2024.02.019
Naive CD8br T Cell Affects Epilepsy through Partial Sphingomyelin Mediation: A Mendelian Randomization StudyPreprint
Wang, J., Kaiji, L. I., Gao, Y., Wu, R., Chen, B., Chen, X., Liu, Y., Liu, H., Zhang, S., Xu, S., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-4529047/v1
Identification of Emerging Drug Targets for Pulmonary Functions Through Mendelian Randomization Analysis of the Plasma ProteomePreprint
Liang, J., Lin, Y., Liu, Y., Lin, H., Xie, Z., Wu, T., Zhang, X., Zhou, X., Tan, Z., Cheng, Z., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-4635102/v1
Multivariable Mendelian randomization with incomplete measurements on the exposure variables in the Hispanic Community Health Study/Study of Latinos
Li, Y., Wong, K. Y., Howard, A. G., Gordon‐Larsen, P., Highland, H. M., Graff, M., North, K. E., Downie, C. G., Avery, C. L., Yu, B., et al. (2024) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2024.100338
Coffee intake and risk of diabetic retinopathy: a Mendelian randomization studyPreprint
Wu, Y., Ni, Y., & Huang, X. (2024) · Research Square · doi:10.21203/rs.3.rs-4718773/v1
Modifiable risk factors mediating the impact of educational inequality on heart failure: A Mendelian randomization study
Zhou, Y., Ye, R., & Guo, X. (2024) · Preventive Medicine · doi:10.1016/j.ypmed.2024.108098
Causal effect between immunocytes, plasma metabolites, and hepatocellular carcinoma: a bidirectional two-sample Mendelian randomization study and mediation analysisPreprint
Tang, X., Xue, J., Zhang, J., & Zhou, J. (2024) · Research Square · doi:10.21203/rs.3.rs-4740840/v1
Relationship between gut microbiota and breast cancer: a Mendelian randomization analysis of mediating effects based on inflammatory proteinsPreprint
Li, H., Li, H., Liu, Y., Chen, C., Liu, X., & Li, H. (2024) · Research Square · doi:10.21203/rs.3.rs-4667151/v1
Identifying the plasma metabolome responsible for mediating immune cell action in severe COVID-19: a Mendelian randomization investigation
Zhang, Y., Hua, J., & Chen, L. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1393432
Smoking behaviors, physical activities, pulmonary diseases and COVID-19 severity: A Mendelian randomization study
Zheng, X., Chen, M.-B., Zhuang, Y., Xu, J., Zhao, L., Qian, Y., & Shen, W. (2024) · Medicine · doi:10.1097/md.0000000000039416
Causal association between frailty and chronic obstructive pulmonary disease: insights from bidirectional Mendelian randomization and mediation analysisPreprint
Cheng, Z., Wu, J., Xu, C., & Yan, X. (2024) · Research Square · doi:10.21203/rs.3.rs-4869762/v1
Mood swings, abdominal obesity, and heart failure: A Mediation Mendelian Randomization StudyPreprint
Wu, Y., Gao, X., Fang, Q., Shen, T., Tan, J., Li, Q., & Huang, J. Y. (2024) · Research Square · doi:10.21203/rs.3.rs-4879626/v1
Genetic estimation of causalities between educational attainment with common digestive tract diseases and the mediating pathways
Wang, Y., Bi, Y., Wang, Y., Ji, F., & Zhang, L. (2024) · BMC Gastroenterology · doi:10.1186/s12876-024-03400-x
Low-density lipoprotein cholesterol and the risk of hyperemesis gravidarum: a Mendelian randomization study
Liu, X., Zhou, X., Wang, J., Cai, A., Zhang, Y., Zhang, J., Wu, Z. R., & Zhu, B. (2024) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2024.2397722
Gut microbiota, lipids, immunity, and liver disease: Insights from Mendelian Randomization and murine modelsPreprint
Lei, L., lin, J., Liang, Q., Huang, X., Yang, X., shi, W., pan, L., li, W., & Yang, J. (2024) · Research Square · doi:10.21203/rs.3.rs-4961377/v1
Role of double-negative autoreactive cells (CD4−CD8−) in phosphatidylcholine-mediated rheumatoid arthritis: A Mendelian randomization study
Zhao, H., & Ni, L. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e39946
Skimmed milk intake reduces the risk of ER− breast cancer: a Mendelian randomization analysis
Huang, Y., Zhang, W., Chen, J., Qiu, S., Xue, C., & Wu, H. (2024) · Discover Oncology · doi:10.1007/s12672-024-01448-5
Impact of Chronic Pain on Lung Cancer Incidence and Mortality: Evidence from Prospective Observational Studies and Genetic AnalysesPreprint
Xu, J., Li, Z., Wang, Y., Wang, S., Zhang, S., Yang, J., Zhou, T., Zhou, Y., Gao, Z., Sun, H., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.5008751
Causal relationship between ferroptosis-related gene HSPA5 and hepatocellular carcinoma: a study based on mendelian randomization and mediation analysis
Bing, C. U. I., Xu, C., Xu, Y., Aqin, C. H. E. N., Chaoming, M. A. O., & Chen, Y. (2024) · Journal of Zhejiang University (Medical Sciences) · doi:10.3724/zdxbyxb-2024-0095
Casual roles of gut microbiota, immune cells, and inflammatory cytokines in acute respiratory distress syndrome: a two-sample Mendelian randomization study and mediation analysisPreprint
Fan, Y., Chen, J., Zhuang, Y., Chang, L., Wang, W., & Zhang, Y. (2024) · Research Square · doi:10.21203/rs.3.rs-5256332/v1
Platelet indices and idiopathic pulmonary fibrosis: a multivariable mendelian randomization studyPreprint
Zheng, Y., Liang, Y., Zhu, L., Li, C., Zang, N., Wang, T., Pang, L., Lv, X., & Liu, Y. (2024) · Research Square · doi:10.21203/rs.3.rs-5035687/v1
A bidirectional Mendelian randomization study of spleen volume and Crohn disease
Song, H.-H., Zhang, H., Hu, X., & Jiang, X.-C. (2024) · Medicine · doi:10.1097/md.0000000000040515
Causal Effects of Sleep Quality on Primary Headache and the Mediation via Gut Microbiota: A Mendelian Randomization Study
Zhao, H., Guan, D., Ma, Z., Yang, M., Dong, N., & Guo, J. (2024) · Brain and Behavior · doi:10.1002/brb3.70129 · Cited by 1
CD19 on CD20- immune cell causes aortic valve calcification by affecting levels of the plasma metabolite 1-(1-enyl-palmitoyl)-2-arachidonoyl-gpc (p-16:0/20:4): a Mendelian Randomization studyPreprint
Zhou, Q., Yi, S., Liu, S., Wei, W., Zhou, Z., & Yang, B. (2024) · Research Square · doi:10.21203/rs.3.rs-5410795/v1
Exploring the relationship between gut microbiota, immune characteristics, and female genital tract polyps using genetic evidence
Jia, R., Fu, Y., Xue, M., Zhou, C., & Jin, J. (2024) · Medicine · doi:10.1097/md.0000000000040833
Gut microbiota may mediate the causality of statins on diabetic nephropathy: a mediation Mendelian randomization study
Wen, X., & Xu, G. (2024) · International Urology and Nephrology · doi:10.1007/s11255-024-04321-0
ASSOCIATION BETWEEN CIRCADIAN RHYTHMS, SLEEP, AND DEPRESSION: A BIDIRECTIONAL MENDELIAN RANDOMISATION STUDY IN THE UK BIOBANKPreprint
Paz, V., Williams, D. M., Richards, M., Tassino, B., da Silva, A. C. R., & Garfield, V. (2024) · medRxiv · doi:10.1101/2024.12.08.24318680
Regresyon Modeli Kullanılarak Aracı Değişken Analizi: Tarım Verilerinde Uygulaması
Köleoğlu, N., & Çelik, Ş. (2024) · Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi · doi:10.47495/okufbed.1435360
Causal associations of immunophenotypes with metabolic dysfunction-associated fatty liver disease and mediating pathways: a Mendelian randomization study
Xie, K., Chen, M., An, H., Gao, J., Tang, C., & Huang, Z. (2024) · Therapeutic Advances in Chronic Disease · doi:10.1177/20406223241303649
Apolipoprotein and peripheral artery disease: Mendelian randomization analysis
Wan, C.-X., Gong, Y.-S., & Xu, T. (2024) · Vascular · doi:10.1177/17085381241309809
Mendelian randomization evidence for lung function mediates the association between childhood allergies (age <16 years) and essential hypertension
Long, Y., She, J., Guo, F., Zhou, B., Chen, F., Hu, Y. S., Gao, L., & Huang, H. (2024) · Reproductive and Developmental Medicine · doi:10.1097/rd9.0000000000000121
Genetically Predicted Inflammatory Proteins Mediate the Association Between Gut Microbiota and Preterm Delivery: A Mendelian Randomization Study
Zhang, M., Chen, X., Zhang, Y., Huang, J., & Chen, L. (2024) · Medical & Clinical Research · doi:10.33140/mcr.09.12.03
Dietary and Serum Micronutrients Associations with Lung Cancer: Results from the NHANES 1988-2018 and Mendelian randomization studyPreprint
Yi, X., Xie, S., Hu, X., Zhao, W., Ouyang, Y., Zhang, Z., Yang, Z., Huang, X., Wang, L., Peng, M., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-5691131/v1
Is Innovation the Missing Link in the Competitive Advantage of Indonesia's Small and Medium Enterprises in the Fashion Industry?
Fedrerika, F., & Ongkowijoyo, G. (2024) · Petra International Journal of Business Studies · doi:10.9744/petraijbs.7.2.221-234
Adiposity distribution and risks of twelve obesity-related cancers: a Mendelian randomization analysisPreprint
Hazelwood, E., Goudswaard, L. J., Lee, M. A., Vabistsevits, M., Pournaras, D. J., Brenner, H., Buchanan, D. D., Gruber, S. B., Gsur, A., Li, L., et al. (2025) · medRxiv · doi:10.1101/2025.01.10.25320324
Roles of cerebrospinal fluid metabolites in mediating the relationship between cathepsins and narcolepsy type 1: A comprehensive Mendelian randomization analysis
Wu, Y., Gan, Q., Su, X., Ding, Y., Liu, Q., Wang, J., Zhang, Y., Zhang, N., & Wu, K. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111263
Integrative Multi-Omics and Mendelian Randomisation Reveal Key Circulating Mediators Linking Type 2 Diabetes to Coronary AtherosclerosisPreprint
Lin, M., Guo, J., Tang, W., Tao, H., Gu, Z., Zhou, F., Jiang, Y., Zhang, R., Jia, D., Sun, Y., et al. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5112749
Role of Immune Cells in Mediating the Causal Effect of Gut Microbiota on Type 2 Diabetes
Ruifang, L., Ruiting, C., Yang, Z., & Li, C. (2025) · Current Molecular Medicine · doi:10.2174/0115665240322713241114051433
Burden of Dementia Due to Stroke Subtypes: A Study Integrating the GBD Database and Mendelian RandomizationPreprint
Jin, M., Liu, J., Bao, Z., Hong, X., He, S., & Gao, F. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5134427
A Mendelian randomization approach for advancing healthcare innovation: From pregnancy hypertension to schizophrenia
Peng, W., Ran, Q., Wu, F., & Hu, Z. (2025) · Technology and Health Care · doi:10.1177/09287329251316227
Role of Immune Cells in Mediating the Effect of Lipids on Preeclampsia
Dang, C., Duan, Y., Liu, P., Liu, J., Yu, X., & Wang, J. (2025) · Reproductive Sciences · doi:10.1007/s43032-025-01809-7
Causal Relationship Between Intelligence, Noncognitive Education, Cognition and Urinary Tract or Kidney Infection: A Mendelian Randomization Study
Fu, S., Li, Q., Li, C., Wan, S., Wang, Q., Min, Y., Xie, Y., Liu, H., Hu, T., Liu, H., et al. (2025) · International Journal of Nephrology and Renovascular Disease · doi:10.2147/ijnrd.s511736
Observational and genetic evidence highlight the association of modifiable risk factors with the incidence and severity of neuroimmunological disorders
Xia, J., Li, J., Qian, Y., Han, J., Lin, M., Wang, M.-Y., Chen, T., Chai, G., Zhao, Y., & Hao, J. (2025) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2025.100975
The effect of inflammatory proteins on COVID-19 is mediated by blood metabolites: A Mendelian randomization study
Chen, Y., & Chen, C. (2025) · Medicine · doi:10.1097/md.0000000000041852
Immune Cells, Metabolites, and Intracranial Aneurysms: A Mendelian Randomization Study
Hao, W., Liu, C., Zhang, T., Cai, Y., & Wang, Y. (2025) · Journal of Craniofacial Surgery · doi:10.1097/scs.0000000000011238
Sensitivity analysis for causal mediation analysis with Mendelian randomization
Chen, Z., Chen, Y., & Zhang, H. (2024) · JUSTC · doi:10.52396/justc-2023-0055
Exploring the Impact of 731 Immunophenotypes on Alopecia Areata Risk: A Mendelian Randomization Analysis With Plasma Metabolites as Mediators
Wang, C., Wu, C., & Liang, H. (2025) · Journal of Craniofacial Surgery · doi:10.1097/scs.0000000000011291
The active ingredients and targets of Kouqiangjie formula on periodontitis: a multi-approach study
Wu, Y., Li, J., Liu, M., Gao, R., Xie, Y., Li, H., & Li, L. (2025) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-025-03942-1
Genetically-influenced HDL concentration, composition and modulation and the risk of sepsis: a Mendelian Randomization StudyPreprint
Li, M., Kooijman, S., van Dijk, K. W., Kastelein, J. J. P., Rensen, P. C. N., & Noordam, R. (2025) · medRxiv · doi:10.1101/2025.03.31.25324957
Atorvastatin, simvastatin, rosuvastatin and Amyotrophic lateral sclerosis establishing cause and effectPreprint
Li, M., Li, Y., Yang, X., Sun, Y., Huang, Y., & Jiang, L. (2025) · Research Square · doi:10.21203/rs.3.rs-6250968/v1
Effect of the plasma metabolites, biomarkers, and inflammatory proteins on urolithiasis: insights from Mendelian randomization and mediation analysis
Huang, H., Zhi, W., Li, H., Wang, C., Chen, C., Liu, Y., Qin, J., Cao, S., & Yang, X. (2025) · Urolithiasis · doi:10.1007/s00240-025-01738-9
Sedentary lifestyle and hallux valgus: Unraveling the causal pathways and the mediating role of calcium homeostasis through mendelian randomization
Liu, M., Liu, Y., Sun, M., Zeng, Z., Song, Y., Jia, E., & Wu, S. (2025) · The Journal of Foot & Ankle Surgery · doi:10.1053/j.jfas.2025.04.003
Analyzing the causal relationship between gut microbiotas, blood metabolites, and COVID-19 susceptibility: A Mendelian randomization study
Yao, X., Zhang, Y., Weng, Y., Xie, J., & Zheng, K. (2025) · Medicine · doi:10.1097/md.0000000000041445
Relationships among immune cells, metabolites, and non-small cell lung cancer: a mediation Mendelian randomization study
Chen, Y., Wan, X., Zhang, N., Zhang, L., Jiao, J., & Sun, Z. (2025) · Discover Oncology · doi:10.1007/s12672-025-02301-z

Authors: Carter, A. R., Sanderson, E., Hammerton, G., Richmond, R. C., Davey Smith, G., Heron, J., Taylor, A. E., Davies, N. M., & Howe, L. D.
Affiliations: University of Bristol (GB)
University Hospitals Bristol NHS Foundation Trust (GB)
Norwegian University of Science and Technology (NO)
Corresponding author: Carter, Alice R.
ORCID: Carter, Alice R.
Sanderson, Eleanor
Hammerton, Gemma
Richmond, Rebecca C.
Heron, Jon
Taylor, Amy E.
Davies, Neil M.
Howe, Laura D.
Venue: European Journal of Epidemiology
Publisher: Springer Science and Business Media LLC
Published: 2021-05
Volume: 36
Issue: 5
Pages: 465-478
ISSN: 0393-2990 (ISSN-L)
1573-7284
DOI: 10.1007/s10654-021-00757-1
PMC: PMC8159796
OpenAlex: W3159102563
Cited by: 1,215
References: 67
Citations by year: 2026: 196 · 2025: 407 · 2024: 386 · 2023: 143 · 2022: 54 · 2021: 18
FWCI: 117.42
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor, 6 d)
Locations: European Journal of Epidemiology (publishedVersion, cc-by)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Bristol Research (University of Bristol) (submittedVersion, cc-by)
Funders: UK Medical Research Council (MC_UU_00011/1, MR/M020894)
UK Economic and Social Research Council (ES/N000757/1)
Wellcome Trust (209138/Z/17/Z)
Norwegian Research Council (295989)
Topics: Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
Keywords: Mendelian randomization, mediation analysis, causal inference, confounding, measurement error, weak instrument bias, pleiotropy, multiple mediators
MeSH terms: Mediation Analysis, Humans, Genetic Variation, Bias, Causality, Genome-Wide Association Study, Mendelian Randomization Analysis, Genetic Pleiotropy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Mendelian randomisation for mediation analysis: current methods and challenges for implementation

Abstract

Overview

Integrity signals

Figures

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks