ArticlePLoS genetics2022
Noise-augmented directional clustering of genetic association data identifies distinct mechanisms underlying obesity.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: A Mendelian randomisation study.PLoS medicine · 2023Pooled it
- Systemic proteomic dynamics of acute exercise reveal genetic links to health and disease.Nature metabolism · 2026Article
- Article
- Genetic subtyping of obesity reveals biological insights into the uncoupling of adiposity from its cardiometabolic comorbidities.Nature medicine · 2025Article
- Genomics reveals eleven obesity endotypes with distinct biological and phenotypic signatures.medRxiv : the preprint server for health sciences · 2025Article
- Exploring the shared genetic landscape of diabetes and cardiovascular disease: findings and future implications.Diabetologia · 2025Review
- Distinct pathway-based effects of blood pressure and body mass index on cardiovascular traits: comparison of novel Mendelian randomization approaches.Genome medicine · 2025Article
- Article
- Using clustering of genetic variants in Mendelian randomization to interrogate the causal pathways underlying multimorbidity from a common risk factor.Genetic epidemiology · 2025Article
- Roles of naïve CD4Journal of translational medicine · 2024Article
- Systemic proteome adaptions to 7-day complete caloric restriction in humans.Nature metabolism · 2024Article
- A Bayesian approach to Mendelian randomization using summary statistics in the univariable and multivariable settings with correlated pleiotropy.American journal of human genetics · 2024Article
- Using genetic association data to guide drug discovery and development: Review of methods and applications.American journal of human genetics · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Clustering genetic variants based on their associations with different traits can provide insight into their underlying biological mechanisms. Existing clustering approaches typically group variants based on the similarity of their association estimates for various traits. We present a new procedure for clustering variants based on their proportional associations with different traits, which is more reflective of the underlying mechanisms to which they relate. The method is based on a mixture model approach for directional clustering and includes a noise cluster that provides robustness to outliers. The procedure performs well across a range of simulation scenarios. In an applied setting, clustering genetic variants associated with body mass index generates groups reflective of distinct biological pathways. Mendelian randomization analyses support that the clusters vary in their effect on coronary heart disease, including one cluster that represents elevated body mass index with a favourable metabolic profile and reduced coronary heart disease risk. Analysis of the biological pathways underlying this cluster identifies inflammation as potentially explaining differences in the effects of increased body mass index on coronary heart disease.
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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.