ArticleNAR genomics and bioinformatics2020
MR-LDP: a two-sample Mendelian randomization for GWAS summary statistics accounting for linkage disequilibrium and horizontal pleiotropy.
Article in NAR genomics and bioinformatics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
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Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- The harmful effect of ankylosing spondylitis on diabetes mellitus: new evidence from the Mendelian randomization analysis.Frontiers in endocrinology · 2024Pooled it
- Association Between Telomere Length and Skin Cancer and Aging: A Mendelian Randomization Analysis.Frontiers in genetics · 2022Pooled it
- Article
- Genetically Proxied Associations Among 473 Gut Microbial Taxa, 1,400 Circulating Metabolites, and Mental and Behavioral Disorders: A Mendelian Randomization Study.Journal of molecular neuroscience : MN · 2026Article
- Causal effect heterogeneity estimation using summary statistics.Research square · 2026Article
- Linking Processed and Red Meat Consumption to Specific Lung Cancer Subtypes: A Mendelian Randomization Analysis.Current pharmaceutical biotechnology · 2026Article
- RMR-ICP: robust Mendelian randomization method accounting for idiosyncratic and correlated pleiotropy with applications to stroke outcomes.Briefings in bioinformatics · 2025Article
- Genetic prediction of immune cells, inflammatory proteins, and metabolite-mediated association between gut microbiota and COPD: a Mendelian randomization study.Scientific reports · 2025Article
- Genetically predicted immune cells mediates the association between hepatocellular carcinoma and inflammatory proteins: a Mendelian randomization study.Discover oncology · 2025Article
- Genetic prediction of blood metabolites and causal relationships with pain associated with temporomandibular disorders: a Mendelian randomization study.Journal of oral & facial pain and headache · 2025Article
- The Eating Disorders Genetics Initiative 2 (EDGI2): study protocol.BMC psychiatry · 2025Article
- Potential causal association between gut microbiota, inflammatory cytokines, and acute pancreatitis: A Mendelian randomization study.Journal of intensive medicine · 2025Article
- Evaluating the Effect of Telomere Length on Oral and Oropharyngeal Cancer Risk Using Mendelian Randomization.International dental journal · 2025Article
- Investigating the causal relationship between the gut microbiome and rheumatoid arthritis: mediating effects of immune cells.Journal of translational medicine · 2025Article
- Causal associations between iron levels in subcortical brain regions and psychiatric disorders: a Mendelian randomization study.Translational psychiatry · 2025Article
- Exploring the Causal Relationship Between Saliva Microbiota Abundance and Chronic Obstructive Pulmonary Disease/Idiopathic Pulmonary Fibrosis: A Two-Sample Mendelian Randomization Study.International journal of chronic obstructive pulmonary disease · 2025Article
- Gene prediction of immune cells association between gut microbiota and colorectal cancer: a Mendelian randomization study.Frontiers in immunology · 2025Article
- Advances in Mendelian Randomization Studies of Obesity Over the Past Decade: Uncovering Key Genetic Mechanisms.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- The goldmine of GWAS summary statistics: a systematic review of methods and tools.BioData mining · 2024Article
- A robust cis-Mendelian randomization method with application to drug target discovery.Nature communications · 2024Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proliferation of genome-wide association studies (GWAS) has prompted the use of two-sample Mendelian randomization (MR) with genetic variants as instrumental variables (IVs) for drawing reliable causal relationships between health risk factors and disease outcomes. However, the unique features of GWAS demand that MR methods account for both linkage disequilibrium (LD) and ubiquitously existing horizontal pleiotropy among complex traits, which is the phenomenon wherein a variant affects the outcome through mechanisms other than exclusively through the exposure. Therefore, statistical methods that fail to consider LD and horizontal pleiotropy can lead to biased estimates and false-positive causal relationships. To overcome these limitations, we proposed a probabilistic model for MR analysis in identifying the causal effects between risk factors and disease outcomes using GWAS summary statistics in the presence of LD and to properly account for horizontal pleiotropy among genetic variants (MR-LDP) and develop a computationally efficient algorithm to make the causal inference. We then conducted comprehensive simulation studies to demonstrate the advantages of MR-LDP over the existing methods. Moreover, we used two real exposure-outcome pairs to validate the results from MR-LDP compared with alternative methods, showing that our method is more efficient in using all-instrumental variants in LD. By further applying MR-LDP to lipid traits and body mass index (BMI) as risk factors for complex diseases, we identified multiple pairs of significant causal relationships, including a protective effect of high-density lipoprotein cholesterol on peripheral vascular disease and a positive causal effect of BMI on hemorrhoids.
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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.