Evidence map›Paper›PMID 42465935›Full record

ArticlemedRxiv : the preprint server for health sciences2026

Cell-type-specific polygenic risk scores reveal adipocyte-related interactions with lipids in coronary artery disease.

Jiaqi Hu, Leqi Xu, Tianyu Liu, Wangjie Zheng, Hongyu Zhao

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Jiaqi HuDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.ORCID 0000-0002-6317-7730
Leqi XuDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, USA.ORCID 0000-0001-6789-4959
Tianyu LiuProgram of Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.ORCID 0000-0002-9412-6573
Wangjie ZhengDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, USA.ORCID 0009-0009-8448-1852
Hongyu ZhaoDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, USA.ORCID 0000-0003-1195-9607

Funding

Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI Kurt A Schalper · 2015 to 2026
$31.1M
Statistical Methods for Genetic Risk Predictions across Diverse PopulationsR01HG012735 · NHGRI · YALE UNIVERSITY · PI ZHAO, HONGYU · 2022 to 2025
$2.4M
NCI NIH HHS P50 CA196530NHGRI NIH HHS R01 HG012735
6 · The paper itself

Abstract

Background: Genome-wide polygenic risk scores (PRSs) for coronary artery disease (CAD) aggregate genetic effects across the genome and may obscure biologically distinct mechanisms. We aimed to develop cell-type-specific PRSs (csPRSs) using single-cell RNA sequencing (scRNA-seq) data and investigate their interactions with lipids on CAD risk. Methods: Using publicly available scRNA-seq data from human heart tissue, we identified cell-type-specific genes across 13 major cell types and 64 subpopulations and grouped them into 10 cell clusters. Variants from a CAD genome-wide association study (GWAS) were mapped to cluster-specific genes to construct csPRSs for European-ancestry participants from the UK Biobank (UKB). Interactions between csPRSs and lipid-related phenotypes were evaluated using Cox proportional hazards models and stratified analyses, with significant findings further assessed in an internal validation dataset. Results: Distinct interaction patterns with lipid phenotypes were observed across csPRSs. Low-density lipoprotein (LDL)-related lipid traits, including apolipoprotein B (ApoB), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (cholesterol), primarily interacted with adipocytes (Adip), whereas high-density lipoprotein (HDL) traits interacted with endothelial-mesothelial (EC-Meso), fibroblast (FB), and immune-cell csPRSs. Notably, interactions for Adip csPRSs were replicated in internal validation analyses. Conclusions: Cell-type-specific decomposition of genome-wide PRSs for CAD identified biologically distinct lipid interactions that were not captured by the genome-wide PRS. Adipocyte genetic factors may influence how LDL lipids affect CAD risk. These findings highlight the potential of cell-type-informed PRSs to improve the biological interpretation of PRSs and provide insights into the heterogeneous mechanisms underlying CAD.

Indexed as

Coronary artery disease (CAD)Genetic interactionPolygenic risk score (PRS)

Identifiers

PMID42465935
PMCPMC13370605

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

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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.