ArticleNature communications2025
Disentangling associations between complex traits and cell types with seismic.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Deciphering the Genetic Underpinnings of Liver Cirrhosis-Heart Failure Comorbidity Through Multi-Omics: CRIM1 as a Key Endothelial Mediator.International journal of molecular sciences · 2026Article
- Developmental and cellular vulnerabilities underlie genetic architecture of schizophrenia.Molecular psychiatry · 2026Article
- Protein-protein interaction network architecture of human polygenic traits reveals domain-spanning connectivity and evolutionary pressures.Genome biology · 2026Article
- Single-cell and high-resolution spatial profiling of podocytopathies reveals core mechanisms of podocyte injury.Science advances · 2026Article
- Reducing Unmet Needs in Hidradenitis Suppurativa by Including the Hair Follicle Among an Arsenal of Targets.Experimental dermatology · 2026Review
- Multi-Omics Integrative Analysis Identifies the NK Cell-STAT3 Axis as a Shared Immunogenetic Hub Underlying the Comorbidity of Primary Sclerosing Cholangitis and Ulcerative Colitis.Life (Basel, Switzerland) · 2026Article
- Linking Genetic Risk to Disease-Relevant Cellular States via Metacell-Informed Modeling with ICePop.bioRxiv : the preprint server for biology · 2026Article
- Multi-organ single-cell analysis of preferential expression of CAKUT genes.BMC nephrology · 2026Article
- Genetic Architecture of Trans-Laminar Cribrosa Pressure Difference and Primary Open-Angle Glaucoma.Investigative ophthalmology & visual science · 2026Article
- Multiomics Mendelian randomization identifies serpin family G member 1 as a chronic obstructive pulmonary disease modulator.Signal transduction and targeted therapy · 2026Article
- Exploring the molecular link between arecoline exposure and prostate cancer-related alterations: integrative evidence from network toxicology, single-cell transcriptomics, molecular simulation, and experimental validation.Frontiers in pharmacology · 2026Article
- Comprehensive snRNA-Seq Datasets of Human and Mouse Podocytopathy Integrated with GWAS of Microalbuminuria.Scientific data · 2025Article
- Cell-type specific profiling of human entorhinal cortex at the onset of Alzheimer's disease neuropathology.bioRxiv : the preprint server for biology · 2025Article
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Abstract
Integrating single-cell RNA sequencing with Genome-Wide Association Studies (GWAS) can uncover cell types involved in complex traits and disease. However, current methods often lack scalability, interpretability, and robustness. We present seismic, a framework that computes a novel specificity score capturing both expression magnitude and consistency across cell types and introduces influential gene analysis, an approach to identify genes driving each cell type-trait association. Across over 1000 cell-type characterizations at different granularities and 28 polygenic traits, seismic corroborates known associations and uncovers trait-relevant cell groups not apparent through other methodologies. In Parkinson's and Alzheimer's, seismic unveils both cell- and brain-region-specific differences in pathology. Analyzing a pathology-based Alzheimer's GWAS with seismic enables the identification of vulnerable neuron populations and molecular pathways implicated in their neurodegeneration. In general, seismic is a computationally efficient, powerful, and interpretable approach for mapping the relationships between polygenic traits and cell-type-specific expression, offering new insights into disease mechanisms.
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