ArticleNature communications2020
Exploiting horizontal pleiotropy to search for causal pathways within a Mendelian randomization framework.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 4 of them syntheses that pooled it.
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Who cites it
84 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Genetic evidence of the causal relationship between genetically predicted nutrients and psoriatic arthritis.Clinical rheumatology · 2026Pooled it
- Disentangling the inverse relationship between cancer and Alzheimer's or Parkinson's disease: A systematic review on Mendelian randomization studies.Neurobiology of disease · 2025Pooled it
- Multi-Ancestry Mendelian Randomization Reveals Lipid-Associated Genetic Risk Factors for COPD.International journal of chronic obstructive pulmonary disease · 2025Pooled it
- Mendelian randomization reveals no correlations between herpesvirus infection and idiopathic pulmonary fibrosis.PloS one · 2023Pooled it
- TL-HDMR: a transfer learning framework for advancing equitable causal inference reveals metabolic signatures of stroke across multiple ancestries.Briefings in bioinformatics · 2026Article
- Mendelian Randomization Analysis of Human Blood Metabolites and Sensorineural Hearing Loss.Brain and behavior · 2026Article
- Effects of Gut Microbiome and Metabolic Pathways on Obesity: A Two-Sample Mendelian Randomization and Case-Control Study.Iranian journal of biotechnology · 2026Article
- Estimating causal effects of C-reactive protein on disease and health outcomes using multivariable Mendelian randomization adjusting for heritable confounding.International journal of epidemiology · 2026Article
- Associations of genetic variants with gene expression factors reveal biological pathways underlying complex traits.American journal of human genetics · 2026Article
- Dissecting pleiotropy to gain mechanistic insights into human disease.Nature reviews. Genetics · 2026Review
- Lactylation-based machine algorithm combined with multi-omics analysis to predict prognosis in cervical cancer.Oncology letters · 2026Article
- Bidirectional Association between Atrial Fibrillation and Ovarian Cancer: Evidence from the UK Biobank and Mendelian Randomization.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Bidirectional associations of depression, anxiety, sleep disorders, and constipation: insights from Mendelian randomization.Archives of medical science : AMS · 2026Article
- A practical guide for nephrologist peer reviewers: understanding and appraising Mendelian randomization studies.Renal failure · 2025Article
- Multivariate genome-wide analysis reveals shared genetic architecture and brain structural correlates of human cognitive abilities.Scientific reports · 2025Article
- CD5 mediates the link between CD4+ CD39+ activated Treg cells and gastric cancer: A Mendelian randomization study.Medicine · 2025Article
- The Causal Relationship Between Palmitoylation Genes and Parkinson's Disease: A Mendelian Randomization Study.Journal of molecular neuroscience : MN · 2025Article
- Causal relationship between gut microbiota and pituitary neuroendocrine tumors: a bidirectional Mendelian randomization.Discover oncology · 2025Article
- Causal relationship between immune cells and venous thromboembolism: a bidirectional two-sample Mendelian randomization study.Thrombosis journal · 2025Article
- Identification of MEG3 and MAPK3 as potential therapeutic targets for osteoarthritis through multiomics integration and machine learning.Scientific reports · 2025Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
In Mendelian randomization (MR) analysis, variants that exert horizontal pleiotropy are typically treated as a nuisance. However, they could be valuable in identifying alternative pathways to the traits under investigation. Here, we develop MR-TRYX, a framework that exploits horizontal pleiotropy to discover putative risk factors for disease. We begin by detecting outliers in a single exposure-outcome MR analysis, hypothesising they are due to horizontal pleiotropy. We search across hundreds of complete GWAS summary datasets to systematically identify other (candidate) traits that associate with the outliers. We develop a multi-trait pleiotropy model of the heterogeneity in the exposure-outcome analysis due to pathways through candidate traits. Through detailed investigation of several causal relationships, many pleiotropic pathways are uncovered with already established causal effects, validating the approach, but also alternative putative causal pathways. Adjustment for pleiotropic pathways reduces the heterogeneity across the analyses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.