Evidence map›Paper›PMID 42567164›Full record

ArticleCell genomics2026

Polygenic risk scores and plasma proteomics identify cancer-related proteins and trans-regulated protein networks.

Diptavo Dutta, Jingning Zhang, Xinyu Guo, Rosamund Quint, Mary R Rooney, Mitchell J Machiela, Kevin M Brown, Josef Coresh, Alexis J Battle, Elizabeth A Platz and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 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

5 · Who and what money

Authors and funding

11 authors.

Diptavo DuttaIntegrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA. Electronic address: diptavo.dutta@nih.gov.
Jingning ZhangDepartment of Biostatistics, Johns Hopkins University, Baltimore, MD 21205, USA.
Xinyu GuoDepartment of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
Rosamund QuintDepartment of Biostatistics, Johns Hopkins University, Baltimore, MD 21205, USA.
Mary R RooneyDepartment of Epidemiology, Johns Hopkins University, Baltimore, MD 21205, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD 21205, USA.
Mitchell J MachielaIntegrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.
Kevin M BrownLaboratory of Translational Genetics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.
Josef CoreshDepartment of Biostatistics, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Epidemiology, Johns Hopkins University, Baltimore, MD 21205, USA; Optimal Aging Institute, Department of Population Health, New York University Grossman School of Medicine, New York, NY 10003, USA.
Alexis J BattleDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Elizabeth A PlatzDepartment of Epidemiology, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA.
Nilanjan ChatterjeeDepartment of Biostatistics, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA. Electronic address: nchatte2@jhu.edu.

Funding

THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - COORDINATING CENTER - TASK AREA B.2 AND B.375N92022D00001 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COUPER, DAVID · 2022 to 2025
$13.7M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00003 · NHLBI · UNIVERSITY OF MINNESOTA · PI LUTSEY, PAMELA L. · 2022 to 2025
$5.1M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00005 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WAGENKNECHT, LYNNE · 2022 to 2025
$5.0M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00004 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI WINDHAM, BEVERLY GWEN · 2022 to 2025
$4.8M
THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - FIELD CENTER - TASK ORDER 01, TASK AREA A75N92022D00002 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI CORESH, JOSEF · 2022 to 2025
$4.7M
Enhancing ARIC Infrastructure to Yield a New Cancer Epidemiology CohortU01CA164975 · NCI · JOHNS HOPKINS UNIVERSITY · PI PLATZ, ELIZABETH A. · 2012 to 2018
$3.8M
Modeling the dynamicimpact of rare and common genetic variation on gene expression anddiseaseR35GM139580 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI BATTLE, ALEXIS · 2021 to 2025
$3.1M
Profiling Cardiovascular Events and Biomarkers in the Very Old to Improve Personalized Approaches for the Prevention of Cardiac and Vascular DiseaseR01HL134320 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI BALLANTYNE, CHRISTIE MITCHELL, SELVIN, ELIZABETH · 2016 to 2019
$3.1M
Improving diabetes prediction using clinical factors, proteomic biomarkers, and polygenic risk scoresK01DK141963 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI Mary R Rooney · 2025 to 2026
$313k
NCI NIH HHS U01 CA164975NHLBI NIH HHS 75N92022D00001NHLBI NIH HHS 75N92022D00002NHLBI NIH HHS 75N92022D00003NHLBI NIH HHS 75N92022D00004NHLBI NIH HHS 75N92022D00005NHLBI NIH HHS R01 HL134320NIDDK NIH HHS K01 DK141963NIGMS NIH HHS R35 GM139580
6 · The paper itself

Abstract

Genome-wide association studies identify cancer susceptibility loci, but downstream protein mechanisms remain incompletely defined. We integrate polygenic risk scores (PRSs) for 21 cancers with 4,955 plasma proteins measured in cancer-free Atherosclerosis Risk in Communities (ARIC) participants to prioritize cancer-related proteins and protein networks. The protein quantitative trait score (pQTS) approach assesses associations between cancer PRS and individual protein levels, while ARCHIE partitions cancer risk variants into trans-regulated protein-network components using sparse canonical correlation analysis. Across cancers, pQTS identifies 90 protein associations, including 53 distal trans associations, and ARCHIE identifies 19 components spanning 433 proteins. Downstream analyses connect prioritized proteins to cancer driver genes, somatic alterations, immune cell populations, CRISPR dependency, and cancer-relevant pathways. Cervical cancer and basal cell carcinoma illustrate immune, human papillomavirus (HPV)-related, pigmentation, and inflammatory mechanisms. These findings show that PRS-proteome integration can reveal circulating protein networks underlying inherited cancer susceptibility.

Indexed as

Blood ProteinsMultifactorial InheritanceNeoplasmsProtein Interaction MapsProteomicsFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreGenome-Wide Association StudyHumansBlood Proteinscancerpartitioned PRSpolygenic risk scoresproteomicssparse canonical correlationtrans associations

Identifiers

PMID42567164
PMCPMC13576709

What OpenQuestion holds

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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 OpenQuestion graph.