Evidence map›Paper›PMID 39763728›Full record

ArticlebioRxiv : the preprint server for biology2024

Pathway Polygenic Risk Scores (pPRS) for the Analysis of Gene-environment Interaction.

W James Gauderman, Yubo Fu, Bryan Queme, Eric Kawaguchi, Yinqiao Wang, John Morrison, Hermann Brenner, Andrew Chan, Stephen B Gruber, Temitope Keku and 12 more

Registry-linked trialAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02328677 (ColoCare Transdisciplinary Research in Colorectal Cancer Prognosis), which is not on this 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.

NCT02328677 recruitingnot on this map

ColoCare Transdisciplinary Research in Colorectal Cancer Prognosis

TypeobservationalSponsorUniversity of UtahRan2007 to 2030Enrolled5,000ConditionsColorectal Cancer
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

22 authors.

W James GaudermanDivision of Biostatistics, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-6626-9091
Yubo FuDivision of Biostatistics, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
Bryan QuemeDivision of Bioinformatics, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
Eric KawaguchiDivision of Biostatistics, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
Yinqiao WangDivision of Biostatistics, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
John MorrisonDivision of Biostatistics, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID 0000-0002-6129-1572
Andrew ChanClinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Stephen B GruberCenter for Precision Medicine and Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
Temitope KekuUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Li LiDepartment of Family Medicine, UVA Comprehensive Cancer Center, UVA School of Medicine, Charlottesville, VA, USA.ORCID 0000-0003-1802-9517
Victor MorenoOncology Data Analytics Program, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.ORCID 0000-0002-2818-5487
Andrew J PellattIntermountain Health, Salt Lake City, UT, USA.ORCID 0000-0002-0127-9790
Ulrike PetersPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
N Jewel SamadderMayo Clinic Comprehensive Cancer Center, Phoenix, AZ, USA.
Stephanie L SchmitGenomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.ORCID 0000-0001-5931-1194
Cornelia M UlrichHuntsman Cancer Institute, Salt Lake City, UT, USA.
Caroline UmDepartment of Population Science, American Cancer Society, Atlanta, GA, USA.
Anna WuDepartment of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
Juan Pablo LewingerDivision of Biostatistics, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
David A DrewClinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8813-0816
Huaiyu MiDivision of Bioinformatics, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0001-8721-202X

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
SWOG Foreign AccrualsU10CA037429 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BLANKE, CHARLES D., MEYSKENS, FRANK L. · 1985 to 2014
$205.2M
Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, TAMIMI, RULLA M · 2000 to 2019
$77.8M
WOMEN'S HEALTH INITIATIVE - CLINICAL COORDINATING CENTER: TASK AREA B - LONG LIFE STUDY VISIT 2 LIMITED HOME VISIT75N92021D00001 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ANDERSON, GARNET L. · 2021 to 2025
$52.0M
Validity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI FUCHS, CHARLES S · 1991 to 2009
$41.8M
PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROBERT S. SANDLER · 1985 to 2026
$30.5M
Statistical Methods for Integrative Genomics in CancerP01CA196569 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI David V Conti · 2016 to 2026
$25.5M
JH/CIDR Genotyping for Genome-Wide Association StudiesU01HG004438 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2007 to 2011
$24.2M
GENETIC SUSCEPTIBILITY TO CANCER IN MULTIETHNIC COHORTSR01CA063464 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2001 to 2005
$23.2M
Multiethnic Cohort Study of Diet and CancerR37CA054281 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI KOLONEL, LAURENCE N. · 2003 to 2012
$23.2M
Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3M
Intramural NIH HHS Z01 CP010200NCATS NIH HHS KL2 TR000421NCI NIH HHS K05 CA152715NCI NIH HHS K05 CA154337NCI NIH HHS P01 CA033619NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS P01 CA196569NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA042182NCI NIH HHS R01 CA048998NCI NIH HHS R01 CA059045NCI NIH HHS R01 CA060987NCI NIH HHS R01 CA063464NCI NIH HHS R01 CA066635NCI NIH HHS R01 CA072520NCI NIH HHS R01 CA076366NCI NIH HHS R01 CA081488NCI NIH HHS R01 CA097325NCI NIH HHS R01 CA136726NCI NIH HHS R01 CA137178NCI NIH HHS R01 CA143237NCI NIH HHS R01 CA151993NCI NIH HHS R01 CA189184NCI NIH HHS R01 CA197350NCI NIH HHS R01 CA201407NCI NIH HHS R01 CA207371NCI NIH HHS R01 CA242218NCI NIH HHS R01 CA273198NCI NIH HHS R03 CA153323NCI NIH HHS R35 CA197735NCI NIH HHS R35 CA253185NCI NIH HHS R37 CA054281NCI NIH HHS U01 CA074783NCI NIH HHS U01 CA074794NCI NIH HHS U01 CA086308NCI NIH HHS U01 CA093326NCI NIH HHS U01 CA122839NCI NIH HHS U01 CA152753NCI NIH HHS U01 CA167551NCI NIH HHS U01 CA167552NCI NIH HHS U01 CA206110NCI NIH HHS U10 CA037429NCI NIH HHS U19 CA148107NCI NIH HHS U24 CA074794NCI NIH HHS UM1 CA167552NCI NIH HHS UM1 CA182883NCI NIH HHS UM1 CA186107NHGRI NIH HHS U01 HG004438NHGRI NIH HHS U01 HG004446NHLBI NIH HHS 75N92021D00001NHLBI NIH HHS 75N92021D00002NHLBI NIH HHS HHSN268201200008CNHLBI NIH HHS HHSN268201200008INHLBI NIH HHS HHSN268201700006CNIA NIH HHS U01 AG018033NIDDK NIH HHS P30 DK034987NIH HHS S10 OD028685WHI NIH HHS 75N92021D00003WHI NIH HHS 75N92021D00004WHI NIH HHS 75N92021D00005
6 · The paper itself

Abstract

A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e. interacts with, important environmental (E) risk factors. Detection of a PRS by environment (PRS × E) interaction may provide clues to underlying biology and can be useful in developing targeted prevention strategies for modifiable risk factors. The standard PRS may include a subset of variants that interact with E but a much larger subset of variants that affect disease without regard to E. This latter subset will 'water down' the underlying signal in former subset, leading to reduced power to detect PRS × E interaction. We explore the use of pathway-defined PRS (pPRS) scores, using state of the art tools to annotate subsets of variants to genomic pathways. We demonstrate via simulation that testing targeted pPRS × E interaction can yield substantially greater power than testing overall PRS × E interaction. We also analyze a large study (N=78,253) of colorectal cancer (CRC) where E = non-steroidal anti-inflammatory drugs (NSAIDs), a well-established protective exposure. While no evidence of overall PRS × NSAIDs interaction (p=0.41) is observed, a significant pPRS × NSAIDs interaction (p=0.0003) is identified based on SNPs within the TGF-β / gonadotropin releasing hormone receptor (GRHR) pathway. NSAIDS is protective (OR=0.84) for those at the 5

Identifiers

PMID39763728
PMCPMC11702571

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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.