ArticleMolecular medicine (Cambridge, Mass.)2018
Enrichment of B cell receptor signaling and epidermal growth factor receptor pathways in monoclonal gammopathy of undetermined significance: a genome-wide genetic interaction study.
Article in Molecular medicine (Cambridge, Mass.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Oxidative Stress Regulates CDH3 Expression in Lung Cancer Cells via OGG1-Mediated SP1 Binding.Antioxidants (Basel, Switzerland) · 2025Article
- Haplotype analysis identifies functional elements in monoclonal gammopathy of unknown significance.Blood cancer journal · 2024Article
- Single-Cell Discovery and Multiomic Characterization of Therapeutic Targets in Multiple Myeloma.Cancer research · 2023Article
- Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas.International journal of molecular sciences · 2022Article
- Identification of key candidate genes and pathways in multiple myeloma by integrated bioinformatics analysis.Journal of cellular physiology · 2019Article
- Genome-wide association study of monoclonal gammopathy of unknown significance (MGUS): comparison with multiple myeloma.Leukemia · 2019Article
- Germline Risk Contribution to Genomic Instability in Multiple Myeloma.Frontiers in genetics · 2019Review
- Genome-wide interaction and pathway-based identification of key regulators in multiple myeloma.Communications biology · 2019Article
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecent identification of 10 germline variants predisposing to monoclonal gammopathy of undetermined significance (MGUS) explicates genetic dependency of this asymptomatic precursor condition with multiple myeloma (MM). Yet much of genetic burden as well as functional links remain unexplained. We propose a workflow to expand the search for susceptibility loci with genome-wide interaction and for subsequent identification of genetic clusters and pathways.
methodsPolygenic interaction analysis on 243 cases/1285 controls identified 14 paired risk loci belonging to unique chromosomal bands which were then replicated in two independent sets (case only study, 82 individuals; case/control study 236 cases/ 2484 controls). Further investigation on gene-set enrichment, regulatory pathway and genetic network was carried out with stand-alone in silico tools separately for both interaction and genome-wide association study-detected risk loci.
resultsIntronic-PREX1 (20q13.13), a reported locus predisposing to MM was confirmed to have contribution to excess MGUS risk in interaction with SETBP1, a well-established candidate predisposing to myeloid malignancies. Pathway enrichment showed B cell receptor signaling pathway (P < 5.3 × 10
conclusionsWe described novel pathways and variants potentially causal for MGUS. The methodology thus proposed to facilitate our search streamlines risk locus-based interaction, genetic network and pathway enrichment analyses.
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