ArticleEuropean journal of epidemiology2022
Exploring and mitigating potential bias when genetic instrumental variables are associated with multiple non-exposure traits in Mendelian randomization.
Article in European journal of epidemiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Establishing causal relationships between sleep and adiposity traits using Mendelian randomization.Obesity (Silver Spring, Md.) · 2023Pooled it
- Causal genes for osteoporosis: Mendelian randomization analysis with multilayer xQTL data.Medicine · 2026Article
- Proteome-wide genetic study identified therapeutic targets for early-onset and late-onset Alzheimer's disease.International journal of surgery (London, England) · 2026Article
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- Association of programmed cell death with atrial fibrillation risk: A multi-omics Mendelian randomization study.Medicine · 2026Article
- Sex-Stratified Genetic Analyses Mapping the Influences of Sedentary Behaviors and Physical Activity on Female Reproductive Health.Research (Washington, D.C.) · 2026Article
- Interaction between sleep disorder and depression on early onset hypertension: a machine learning modelling approach.Archives of public health = Archives belges de sante publique · 2025Article
- Analysis of spermidine's effect on coronary heart disease risk using bidirectional Mendelian randomization and LC-MS/MS.Hereditas · 2025Article
- Unveiling taurine's protective role in ischemic stroke: insights from bidirectional Mendelian randomization and LC-MS/MS analysis.Genes & nutrition · 2025Article
- The Causal Effect of Iron Traits on Risk of Hypertrophic Scarring: A Two-Sample Mendelian Randomization Study.Journal of cosmetic dermatology · 2025Article
- Association between allopurinol and hepatocellular carcinoma: analysis of genetic risk and patient survival.Discover oncology · 2025Article
- Mendelian randomization of plasma proteomics identifies novel ALS-associated proteins and their GO enrichment and KEGG pathway analyses.BMC neurology · 2025Article
- Insights Into Causal Effects of Genetically Proxied Lipids and Lipid-Modifying Drug Targets on Cardiometabolic Diseases.Journal of the American Heart Association · 2025Article
- Genetically determined physical activity levels, sedentary behaviours, and their association with the risk of age-related macular degeneration.The Journal of international medical research · 2025Article
- Celiac Disease and Skin Diseases: A Bidirectional Mendelian Randomization Study.Clinical, cosmetic and investigational dermatology · 2025Article
- The Effect of Epigenetic Age Acceleration on Atopic Dermatitis: A Mendelian Randomization Study.Clinical, cosmetic and investigational dermatology · 2025Article
- Causal relationships between Alzheimer's disease and metabolic dysfunction associated with fatty liver disease: insights from bidirectional network Mendelian Randomization analysis.Metabolomics : Official journal of the Metabolomic Society · 2024Article
- Letter to the editor Regarding 'Causal relationship between basal metabolic rate and intervertebral disc degeneration: a Mendelian randomization study' by Liu Z, et al. (Eur Spine J. 2024 Jun 24. Doi: 10.1007/s00586-024-08367-7).European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2024Article
- Blood metabolites, neurocognition and psychiatric disorders: a Mendelian randomization analysis to investigate causal pathways.Translational psychiatry · 2024Article
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Abstract
With the increasing size and number of genome-wide association studies, individual single nucleotide polymorphisms are increasingly found to associate with multiple traits. Many different mechanisms could result in proposed genetic IVs for an exposure of interest being associated with multiple non-exposure traits, some of which could bias MR results. We describe and illustrate, through causal diagrams, a range of scenarios that could result in proposed IVs being related to non-exposure traits in MR studies. These associations could occur due to five scenarios: (i) confounding, (ii) vertical pleiotropy, (iii) horizontal pleiotropy, (iv) reverse causation and (v) selection bias. For each of these scenarios we outline steps that could be taken to explore the underlying mechanism and mitigate any resulting bias in the MR estimation. We recommend MR studies explore possible IV-non-exposure associations across a wider range of traits than is usually the case. We highlight the pros and cons of relying on sensitivity analyses without considering particular pleiotropic paths versus systematically exploring and controlling for potential pleiotropic or other biasing paths via known traits. We apply our recommendations to an illustrative example of the effect of maternal insomnia on offspring birthweight in UK Biobank.
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