Evidence map›Paper›PMID 41300981›Full record

ArticleCancers2025

Whole-Exome Sequencing-Based Linkage Analysis of Multiple Myeloma (MM) and Monoclonal Gammopathy of Undetermined Significance (MGUS) Pedigrees.

Alyssa I Clay-Gilmour, Nicola J Camp, Xiaomu Wei, Angel Earle, Aaron Norman, Jason Sinnwell, Delphine Demangel, Rosalie Griffin, Charles Dumontet, James McKay and 9 more

Abstract read
In one paragraph

Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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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

19 authors.

Alyssa I Clay-GilmourDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.
Nicola J CampHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0002-4788-1998
Xiaomu WeiWeill Cornell College of Medicine, University of Cornell, New York, NY 10021, USA.
Angel EarleDepartment of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.
Aaron NormanDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-4208-2708
Jason SinnwellDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0003-1964-5522
Delphine DemangelCentre de Recherche en Cancérologie de Lyon/Hospices Civils de Lyon, Université Claude Bernard, 69373 Lyon, France.
Rosalie GriffinDepartment of Epidemiology, Cancer Cancer Prevention and Population Sciences Sciences Division, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0009-0007-5721-3727
Charles DumontetCentre de Recherche en Cancérologie de Lyon/Hospices Civils de Lyon, Université Claude Bernard, 69373 Lyon, France.
James McKayInternational Agency for Research on Cancer, World Health Organization, 69366 Lyon, France.
Ken OffitMemorial Sloan Kettering Cancer Center, New York, NY 60637, USA.ORCID 0000-0002-2180-2032
Vijai JosephMemorial Sloan Kettering Cancer Center, New York, NY 60637, USA.ORCID 0000-0002-7933-151X
Siwei ChenDepartment of Human Genetics, The University of Chicago, Chicago, NY 60637, USA.
Daniel O'BrienDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.
Vincent RajkumarDivision of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
Robert KleinIcahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0003-3539-5391
Shaji KumarDivision of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
Steve LipkinWeill Cornell College of Medicine, University of Cornell, New York, NY 10021, USA.ORCID 0000-0002-0603-9139
Celine M VachonDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Project 4: Targeting Resistance to T-Cell Directed Therapy in Multiple MyelomaP50CA186781 · NCI · MAYO CLINIC ARIZONA · PI Yi Lin · 2015 to 2026
$25.5M
Mayo Cancer Genetic Epidemiology Training ProgramR25CA092049 · NCI · MAYO CLINIC ROCHESTER · PI PETERSEN, GLORIA M., VACHON, CELINE M · 2001 to 2018
$5.3M
Prevalence and Progression of Monoclonal GammopathiesR01CA107476 · NCI · MAYO CLINIC ROCHESTER · PI KUMAR, SHAJI KUNNATHU, RAJKUMAR, S VINCENT · 2004 to 2018
$4.6M
Onset and biomarkers for progression of monoclonal gammopathiesR01CA168762 · NCI · MAYO CLINIC ROCHESTER · PI KUMAR, SHAJI KUNNATHU, RAJKUMAR, S VINCENT · 2012 to 2024
$3.2M
InterLymph Consortium: interrogating pleiotropy and gene by environment interactions among hematopoietic malignancies.U01CA257679 · NCI · INTERNATIONAL AGENCY FOR RES ON CANCER · PI CLAY-GILMOUR, ALYSSA IONE, HJALGRIM, HENRIK · 2021 to 2025
$2.7M
Genetics of Common Cancers: Discovery to ImplementationF99CA234943 · NCI · UNIVERSITY OF UTAH · PI GRIFFIN, ROSALIE · 2018 to 2019
$69k
Fondation Française pour la Recherche contre le Myélome et les Gammapathies NAInstitut National du Cancer 2010-077National Institute of Health NIH Loan Repayment ProgramNCI NIH HHS F99 CA234943NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA186781NCI NIH HHS R01 CA107476NCI NIH HHS R01 CA168762NCI NIH HHS R25 CA092049NCI NIH HHS R25CA092049NCI NIH HHS U01 CA257679NCI NIH HHS U01 CA271014-01World Health Organization 001
6 · The paper itself

Abstract

BACKGROUND/

objectivesFamily history is a known risk factor for multiple myeloma (MM) and its precursor condition, monoclonal gammopathy of undetermined significance (MGUS). Previous genome-wide association studies (GWASs) have identified 35 common loci associated with MM risk and 21 associated with MGUS. The objective of this study was to identify less common and rare genetic loci predisposing to MM/MGUS through whole-exome sequencing (WES)-based linkage analysis.

methodsMultipoint linkage analysis was conducted using the Multipoint Engine for Rapid Likelihood Inference (MERLIN) with the Lander-Green algorithm on germline WES data from 79 pedigrees with 2 or more affected relatives (120 MM, 86 MGUS, and 21 unaffected). Genome-wide linkage was evaluated using 12,946 independent single-nucleotide variants (linkage disequilibrium r

resultsSignificant linkage was observed at chromosome 6q22.33-q24.2 by the non-parametric model (logarithm-of-odds (LOD) = 3.3) and suggestive linkage by the dominant parametric model (heterogeneity LOD (HLOD) = 2.5). Fourteen rare variants within this region were prioritized using family-specific partial LOD scores and in silico functional prediction tools. Nine of these variants,

conclusionsThis study demonstrates the utility of applying a linkage analysis framework to familial WES data for identifying genomic regions and candidate genes that may contribute to MM/MGUS predisposition. These findings provide new insight into the inherited risk and etiology of familial MM and MGUS.

Indexed as

family studylinkage analysismonoclonal gammopathy of undetermined significancemultiple myelomawhole-exome sequencing

Identifiers

PMID41300981
PMCPMC12651453

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