ArticlePLoS genetics2019
Reverse GWAS: Using genetics to identify and model phenotypic subtypes.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- Discerning asthma endotypes through comorbidity mapping.Nature communications · 2022Pooled it
- Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information.Biological psychiatry · 2022Pooled it
- The Use of Population Isolates to Identify Metabolic Syndrome's Genetic Aetiology.Molecular genetics & genomic medicine · 2026Review
- Context-specific genetic effects inform endotypes and treatment in asthma.The Journal of allergy and clinical immunology · 2026Article
- ReverseGWAS identifies combined phenotypes associated with a genotype in GWA studies.Bioinformatics (Oxford, England) · 2026Article
- Depression genetics through the lens of age at onset.Nature genetics · 2025Article
- Red Blood Cell-Related Phenotype-Genotype Correlations in Chronic and Acute Critical Illnesses (Traumatic Brain Injury Cohort and COVID-19 Cohort).International journal of molecular sciences · 2025Article
- Phenotype integration improves power and preserves specificity in biobank-based genetic studies of major depressive disorder.Nature genetics · 2023Article
- Identification of Novel Metabolic Subtypes Using Multi-Trait Limited Mixed Regression in the Chinese Population.Biomedicines · 2022Article
- Ten challenges for clinical translation in psychiatric genetics.Nature genetics · 2022Review
- Open problems in human trait genetics.Genome biology · 2022Review
- Mendelian randomization highlights significant difference and genetic heterogeneity in clinically diagnosed Alzheimer's disease GWAS and self-report proxy phenotype GWAX.Alzheimer's research & therapy · 2022Article
- Vascular Injury in the Zebrafish Tail Modulates Blood Flow and Peak Wall Shear Stress to Restore Embryonic Circular Network.Frontiers in cardiovascular medicine · 2022Article
- Review
- Transcriptome-wide association study of treatment-resistant depression and depression subtypes for drug repurposing.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Multitrait GWAS to connect disease variants and biological mechanisms.PLoS genetics · 2021Article
- Polygenic risk modeling with latent trait-related genetic components.European journal of human genetics : EJHG · 2021Article
- Leveraging eQTLs to identify individual-level tissue of interest for a complex trait.PLoS computational biology · 2021Article
- A model and test for coordinated polygenic epistasis in complex traits.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Characterizing the effect of background selection on the polygenicity of brain-related traits.Genomics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Recent and classical work has revealed biologically and medically significant subtypes in complex diseases and traits. However, relevant subtypes are often unknown, unmeasured, or actively debated, making automated statistical approaches to subtype definition valuable. We propose reverse GWAS (RGWAS) to identify and validate subtypes using genetics and multiple traits: while GWAS seeks the genetic basis of a given trait, RGWAS seeks to define trait subtypes with distinct genetic bases. Unlike existing approaches relying on off-the-shelf clustering methods, RGWAS uses a novel decomposition, MFMR, to model covariates, binary traits, and population structure. We use extensive simulations to show that modelling these features can be crucial for power and calibration. We validate RGWAS in practice by recovering a recently discovered stress subtype in major depression. We then show the utility of RGWAS by identifying three novel subtypes of metabolic traits. We biologically validate these metabolic subtypes with SNP-level tests and a novel polygenic test: the former recover known metabolic GxE SNPs; the latter suggests subtypes may explain substantial missing heritability. Crucially, statins, which are widely prescribed and theorized to increase diabetes risk, have opposing effects on blood glucose across metabolic subtypes, suggesting the subtypes have potential translational value.
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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 Socratic graph.