Evidence map›Paper›PMID 42758802›Full record

ArticlePLoS genetics2026

Identifying shared polygenic risk across cancers.

Jiaqi Hu, Maiyier Muheyati, Leqi Xu, Andrew DeWan, Hongyu Zhao

Abstract read
In one paragraph

Article in PLoS genetics, 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, ConnecticutUnited States of America.ORCID https://orcid.org/0000-0002-6317-7730
Maiyier MuheyatiDepartment of Biostatistics, Yale School of Public Health, New Haven, Connecticut, United States of America.ORCID https://orcid.org/0009-0009-5909-2476
Leqi XuDepartment of Biostatistics, Yale School of Public Health, New Haven, Connecticut, United States of America.
Andrew DeWanDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, ConnecticutUnited States of America.
Hongyu ZhaoDepartment of Biostatistics, Yale School of Public Health, New Haven, Connecticut, United States of America.ORCID https://orcid.org/0000-0003-1195-9607

Funding

Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI KATERINA Abigail POLITI · 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

backgroundShared genetic susceptibility across cancers has been reported but is generally modest at the genome-wide level. Whether such shared polygenic risk exhibits structured convergence at regional or functional levels remains unclear. We investigated shared genetic risk across cancers by integrating local genetic correlation analyses with cross-cancer polygenic risk score (PRS) associations.

methodsWe estimated pairwise local genetic correlations across 16 specific cancers and one pan-cancer phenotype using SUPERGNOVA. Genome regions harboring multiple cancers with mutually correlated local genetic effects were annotated using genetic correlations with non-cancer phenotypes and associations from the GWAS Catalog. In parallel, cross-cancer PRS associations were evaluated, and significant cancer pairs were identified. Genome-wide PRSs for selected pairs were further decomposed into pleiotropy-informed and pathway-specific components to assess functional enrichment of shared polygenic risk.

resultsGenome-wide genetic correlation analyses identified 20 significantly correlated cancer pairs, whereas local analyses revealed 82 regions with shared genetic signals across 66 cancer pairs. Five regions exhibited mutually correlated cancer clusters, with enrichment in functional domains such as inflammatory functions. Cross-cancer PRS analyses identified five cancer pairs with shared polygenic risk. Decomposition of PRSs indicated that these cross-cancer associations were enriched in specific pleiotropy groups and immune-related pathways rather than reflecting diffuse genome-wide overlap.

conclusionOur findings demonstrate that although shared genetic susceptibility across cancers is limited at the genome-wide level, it becomes evident when examined at regional and polygenic scales. Integrating local genetic correlation and PRS decomposition analyses reveals structured patterns of shared genetic risk, providing a framework for investigating cross-cancer polygenic susceptibility.

Indexed as

Genetic Predisposition to DiseaseMultifactorial InheritanceNeoplasmsGenetic PleiotropyGenetic Risk ScoreGenome-Wide Association StudyHumansPhenotypePolymorphism, Single Nucleotide

Identifiers

PMID42758802
PMCPMC13600620

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.