ArticleNature genetics2017
A method for identifying genetic heterogeneity within phenotypically defined disease subgroups.
Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide search for genes affecting the age at diagnosis of type 1 diabetes.Journal of internal medicine · 2021Pooled it
- Context-specific genetic effects inform endotypes and treatment in asthma.The Journal of allergy and clinical immunology · 2026Article
- Depression genetics through the lens of age at onset.Nature genetics · 2025Article
- Epigenetic patient stratification reveals a sub-endotype of type 2 asthma with altered B-cell response.medRxiv : the preprint server for health sciences · 2025Article
- Distinct genetic liability profiles define clinically relevant patient strata across common diseases.Nature communications · 2024Article
- Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder.Nature genetics · 2024Article
- Factorizing polygenic epistasis improves prediction and uncovers biological pathways in complex traits.American journal of human genetics · 2023Article
- E96V Mutation in theInternational journal of molecular sciences · 2023Article
- Rs864745 inFrontiers in endocrinology · 2022Article
- A fast wavelet-based functional association analysis replicates several susceptibility loci for birth weight in a Norwegian population.BMC genomics · 2021Article
- FKBP5 Genotype Linked to Combined PTSD-Depression Symptom in Chinese Earthquake Survivors.Canadian journal of psychiatry. Revue canadienne de psychiatrie · 2019Article
- Reverse GWAS: Using genetics to identify and model phenotypic subtypes.PLoS genetics · 2019Article
- A Bayesian mixture modelling approach for spatial proteomics.PLoS computational biology · 2018Article
- Late-Onset Crohn's Disease Is A Subgroup Distinct in Genetic and Behavioral Risk Factors With UC-Like Characteristics.Inflammatory bowel diseases · 2018Article
- Combining controls can improve power in two-stage association studies.BMC genetics · 2018Article
- Pleiotropic mapping and annotation selection in genome-wide association studies with penalized Gaussian mixture models.Bioinformatics (Oxford, England) · 2018Article
- Embracing polygenicity: a review of methods and tools for psychiatric genetics research.Psychological medicine · 2018Review
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Many common diseases show wide phenotypic variation. We present a statistical method for determining whether phenotypically defined subgroups of disease cases represent different genetic architectures, in which disease-associated variants have different effect sizes in two subgroups. Our method models the genome-wide distributions of genetic association statistics with mixture Gaussians. We apply a global test without requiring explicit identification of disease-associated variants, thus maximizing power in comparison to standard variant-by-variant subgroup analysis. Where evidence for genetic subgrouping is found, we present methods for post hoc identification of the contributing genetic variants. We demonstrate the method on a range of simulated and test data sets, for which expected results are already known. We investigate subgroups of individuals with type 1 diabetes (T1D) defined by autoantibody positivity, establishing evidence for differential genetic architecture with positivity for thyroid-peroxidase-specific antibody, driven generally by variants in known T1D-associated genomic regions.
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