ArticleNature communications2024
PheWAS-based clustering of Mendelian Randomisation instruments reveals distinct mechanism-specific causal effects between obesity and educational attainment.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Cardiovascular diseases and depression: A meta-analysis and Mendelian randomization analysis.Molecular psychiatry · 2025Pooled it
- Testing the causal relationships of physical activity and sedentary behaviour with mental health and substance use disorders: a Mendelian randomisation study.Molecular psychiatry · 2023Pooled it
- Refining Genetic Instruments for Dietary Intake Mendelian Randomization Using Phenome-Wide Association Studies.Genetic epidemiology · 2026Article
- Review
- Genetic clusters of BMI reveal symptom-specific causal effects on depression.Molecular psychiatry · 2026Article
- Challenges and future directions for Mendelian randomization.Nature genetics · 2026Review
- 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
- Causal effect heterogeneity estimation using summary statistics.Research square · 2026Article
- Association Between Metabolic Score for Insulin Resistance (METS-IR) and Risk of Infertility: Evidence from NHANES 2013-2020 and Mendelian Randomization Study.International journal of women's health · 2026Article
- The effect of type 2 diabetes genetic predisposition on non-cardiovascular comorbidities.Nature communications · 2025Article
- STING inhibits the progression of esophageal squamous cell carcinoma by suppressing CPT1A-mediated fatty acid β-oxidation.Acta pharmacologica Sinica · 2025Article
- MR-link-2: pleiotropy robust cis Mendelian randomization validated in three independent reference datasets of causality.Nature communications · 2025Article
- Incorporating genetic data improves target trial emulations and informs the use of polygenic scores in randomized controlled trial design.Nature genetics · 2025Article
- Dietary Intake Mendelian Randomization: Assessment and Development of Methods for Instrument Selection and Robust Inference.medRxiv : the preprint server for health sciences · 2025Article
- Disentangling the effects of nicotine versus non-nicotine constituents of tobacco smoke on major depressive disorder: A multivariable Mendelian randomisation study.Addiction (Abingdon, England) · 2025Article
- Distinct pathway-based effects of blood pressure and body mass index on cardiovascular traits: comparison of novel Mendelian randomization approaches.Genome medicine · 2025Article
- Article
- The effect of type 2 diabetes genetic predisposition on non-cardiovascular comorbidities.medRxiv : the preprint server for health sciences · 2025Article
- A Causal Effect of Serum 25(OH)D Level on Appendicular Muscle Mass: Evidence From NHANES Data and Mendelian Randomization Analyses.Journal of cachexia, sarcopenia and muscle · 2025Article
- Article
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Abstract
Mendelian Randomisation (MR) estimates causal effects between risk factors and complex outcomes using genetic instruments. Pleiotropy, heritable confounders, and heterogeneous causal effects violate MR assumptions and can lead to biases. To alleviate these, we propose an approach employing a Phenome-Wide association Clustering of the MR instruments (PWC-MR) and apply this method to revisit the surprisingly large apparent causal effect of body mass index (BMI) on educational attainment (EDU): [Formula: see text] = -0.19 [-0.22, -0.16]. First, we cluster 324 BMI-associated genetic instruments based on their association with 407 traits in the UK Biobank, which yields six distinct groups. Subsequent cluster-specific MR reveals heterogeneous causal effect estimates on EDU. A cluster enriched for socio-economic indicators yields the largest BMI-on-EDU causal effect estimate ([Formula: see text] = -0.49 [-0.56, -0.42]) whereas a cluster enriched for body-mass specific traits provides a more likely estimate ([Formula: see text] = -0.09 [-0.13, -0.05]). Follow-up analyses confirms these findings: within-sibling MR ([Formula: see text] = -0.05 [-0.09, -0.01]); MR for childhood BMI on EDU ([Formula: see text] = -0.03 [-0.06, -0.002]); step-wise multivariable MR ([Formula: see text] = -0.05 [-0.07, -0.02]) where socio-economic indicators are jointly modelled. Here we show how the in-depth examination of the BMI-EDU causal relationship demonstrates the utility of our PWC-MR approach in revealing distinct pleiotropic pathways and confounder mechanisms.
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