ArticleAmerican journal of human genetics2025
Single-cell transcriptome-wide Mendelian randomization and colocalization analyses uncover cell-specific mechanisms in atherosclerotic cardiovascular disease.
Article in American journal of human genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Proteome-wide Mendelian randomisation identifies causal links between blood proteins and myopia.Journal of global health · 2026Pooled it
- Polyamide-66 microplastics and early-onset ischemic stroke: a systems toxicology, multi-omics, and molecular dynamics simulation analysis.Molecular diversity · 2026Article
- Migraine immune cell gene targets and their relationship to psychiatric disorders.The journal of headache and pain · 2026Article
- From GWAS Signals to Molecular Mechanisms: Explainable AI for Causal Gene Prioritization and Biomolecular Target Interpretation.Biomolecules · 2026Review
- Cardiovascular Genetic Epidemiology in the Genome-Wide Era: From Association Discovery to Mechanistic Dissection and Clinical Translation.Cardiovascular drugs and therapy · 2026Review
- Fatty Acid Metabolism in Health and Cancer: From Fundamental Mechanisms to Therapeutic Application.MedComm · 2026Review
- Dissecting Immune Mechanisms Underlying Sarcopenia Using Multi-omics Approaches.Calcified tissue international · 2026Article
- Multi-Omics and Single-Cell Mendelian Randomization Reveal a Potential Role ofWorld journal of oncology · 2026Article
- Causal effects of gut microbiota and blood metabolites on subtypes of perinatal depression classified based on depressive symptom trajectories: a mendelian randomization study.Nutrition & metabolism · 2026Article
- Macrophages in human atherosclerotic plaques in the era of single-cell and spatial transcriptomics.ImmunoHorizons · 2026Review
- The crotonylation reader DPF2 promotes the development and progression of colon adenocarcinoma through cell-type-specific immune regulation and metabolic reprogramming.Frontiers in pharmacology · 2026Article
- Variant-to-Biomarker Pathways in Peripheral Artery Disease: Multiomics Integration and Clinical Translation.Human mutation · 2026Review
- From trigeminal ganglion to cortex: ATG7 emerges as a key integrator of migraine pathways via multi-omics profiling.The journal of headache and pain · 2025Article
- TRIB3 Links Endoplasmic Reticulum Stress to Impaired Efferocytosis in Atherosclerosis.Circulation research · 2025Article
- Genome-wide association study for circulating metabolic traits in 619,372 individuals.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies (GWASs) have identified numerous genetic loci influencing human disease risk; however, linking these to causal genes remains challenging, limiting opportunities for drug target discovery. Transcriptome-wide association studies (TWASs) address this by linking variants to gene expression but typically rely on bulk RNA sequencing, limiting cell-specific resolution. Here, we present a single-cell TWAS pipeline combining cis-Mendelian randomization (MR) with colocalization analyses at the single-cell level. As a case study, we examined how genetically proxied gene expression in immune cells influences atherosclerotic cardiovascular disease (ASCVD) risk. We integrated single-cell expression quantitative trait loci (sc-eQTLs) for 14 immune cell types with GWASs for coronary artery disease, large artery atherosclerotic stroke, and peripheral artery disease. sc-cis-MR revealed 440 gene-outcome associations across cell types, 88% of which were missed by bulk TWASs, despite the considerably smaller sample size of the sc-eQTL dataset. Of these associations, 21 were replicated with external cis-eQTLs and colocalized with ASCVD GWAS signals. Expanding on previous evidence linking genetically proxied LIPA expression in whole blood to coronary artery disease, we found genetic variants influencing LIPA expression, particularly in monocytes, to drive associations with coronary artery disease, large artery atherosclerotic stroke, and subclinical atherosclerosis traits. A phenome-wide association study confirmed these findings without evidence of associations with unexpected clinical outcomes. scRNA sequencing and immunohistochemistry of human carotid plaques revealed high LIPA expression in plaque macrophages. Our pipeline enables the discovery of cell-specific expression patterns that drive genetic predisposition to human disease, potentially impacting target selection for cell-tailored therapeutics.
Indexed as
Identifiers
What Socratic holds
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.