ArticleInternational journal of epidemiology2023
An empirical investigation into the impact of winner's curse on estimates from Mendelian randomization.
Article in International journal of epidemiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
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- Checking Genetic Homogeneity Between Two Samples Using Summary Statistics With Application to Mendelian Randomization.Statistics in medicine · 2026Article
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- Sex-specific roles of insulin-like growth factor-1, lean mass and fat mass in type 2 diabetes prevention: Mendelian randomization studies in Western and East Asian populations.Cardiovascular diabetology. Endocrinology reports · 2026Article
- Integrative proteogenomic and observational analysis identifies potential biomarkers for latent autoimmune diabetes in adults.Cardiovascular diabetology · 2026Observational
- Simulated sample splitting approach to address biases due to instrument selection and participant overlap in two-sample Mendelian Randomization studies.PLoS genetics · 2026Article
- Iron status modulates immune cell proportions to drive epigenetic age acceleration: A 2-step Mendelian randomization study.Medicine · 2026Article
- Transfer learning-based two-sample Mendelian randomization method for heterogeneous population.Briefings in bioinformatics · 2026Article
- Mendelian Randomization Methods for Causal Inference: Estimands, Identification and Inference.Statistics in medicine · 2026Review
- Plasma Proteome-Wide Mendelian Randomization with Multi-Layer Triangulation Identifies Druggable Targets for Uterine Leiomyoma.International journal of women's health · 2026Article
- Alcohol consumption and risk of cancer: a Mendelian randomization analysis of four biobanks and consortium data.BMC medicine · 2025Article
- Genetic Evidence Supporting a Role for Brain Region Volume and Functional Network Alterations in Major Depression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Comprehensive analysis of Mendelian randomization and scRNA-seq identify key prognostic genes and relevant functional roles in colorectal cancer.Scientific reports · 2025Article
- Blood metabolic biomarkers and colorectal cancer risk: results from large prospective cohort and Mendelian randomisation analyses.British journal of cancer · 2025Article
- Application of Human Genetics to Prioritize Coagulation Cascade Protein Targets for Ischemic Stroke Prevention.Stroke · 2025Article
- Causal association of circulating immune cells with nephrotic syndrome: evidence from a two-sample Mendelian randomization study.International urology and nephrology · 2025Article
- Comprehensive analysis of molecular, physiological, and functional biomarkers of aging with neurological diseases using Mendelian randomization.GeroScience · 2025Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
introductionGenetic associations for variants identified through genome-wide association studies (GWASs) tend to be overestimated in the original discovery data set as, if the association was underestimated, the variant may not have been detected. This bias, known as winner's curse, can affect Mendelian randomization estimates, but its severity and potential impact are unclear.
methodsWe performed an empirical investigation to assess the potential bias from winner's curse in practice. We considered Mendelian randomization estimates for the effect of body mass index (BMI) on coronary artery disease risk. We randomly divided a UK Biobank data set 100 times into three equally sized subsets. The first subset was treated as the 'discovery GWAS'. We compared genetic associations estimated in the discovery GWAS to those estimated in the other subsets for each of the 100 iterations.
resultsFor variants associated with BMI at P < 5 × 10-8 in at least one iteration, genetic associations with BMI were up to 5-fold greater in iterations in which the variant was associated with BMI at P < 5 × 10-8 compared with its mean association across all iterations. If the minimum P-value for association with BMI was P = 10-13 or lower, then this inflation was <25%. Mendelian randomization estimates were affected by winner's curse bias. However, bias did not materially affect results; all analyses indicated a deleterious effect of BMI on coronary artery disease risk.
conclusionsWinner's curse can bias Mendelian randomization estimates, although its practical impact may not be substantial. If avoiding sample overlap is infeasible, analysts should consider performing a sensitivity analysis based on variants strongly associated with the exposure.
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