Genome-wide meta-analysis of monoclonal gammopathy of undetermined significance (MGUS) identifies risk loci impacting IRF-6
Year: 2022
Type: review
Study design: Observational Study
Abstract: Monoclonal gammopathy of undetermined significance (MGUS) is a benign plasma cell disorder, common in the Western population (3–5% ≥50 years) and characterized by an asymptomatic clonal plasma cell expansion [ 1 ]. MGUS progresses to multiple myeloma (MM) at a rate of 1% per year [ 1 ], but can also progress to light chain amyloidosis (AL amyloidosis), Waldenström macroglobulinemia, and lymphoma. Familial clustering of MGUS or MM support the role for genetic susceptibility [ 2 ]. MM and MGUS have shared heritability, with a genetic correlation of 55% and SNP-based heritability estimates of 17% and 15%, respectively (3,4). This suggests a large portion of missing heritability to be identified. Previous genome-wide association studies (GWAS) have successfully identified 24 common loci associated with MM risk [ 3 , 4 ]; of these, 12 are also associated with MGUS [ 5 ]. Twenty additional loci have been identified for risk of MGUS but the impact of these loci on progression is unknown [ 5 , 6 ]. Identifying additional common variants contributing to MGUS may elucidate the unaccounted missing heritability for both MGUS and MM. Further, understanding genetic determinants of MGUS are important regardless of MM, given the associations of MGUS with multiple conditions, not just MM. In this study, we performed the largest MGUS GWAS meta-analysis to date and validated associations of known MM/MGUS risk variants.
Source: Blood Cancer Journal
Authors: Alyssa Clay-Gilmour, Subhayan Chattopadhyay, Michelle A. T. Hildebrandt, Hauke Thomsen, Niels Weinhold, Pavel Vodicka, Ludmila Vodickova, Per Hoffmann, Markus M. Nöthen, Karl-Heinz Jöckel, Börge Schmidt, Christian Langer, Roman Hajek, Göran Hallmans, Ulrika Pettersson-Kymmer, Claes Ohlsson, Florentin Späth, Richard Houlston, Hartmut Goldschmidt, Elisabet E. Manasanch, Aaron Norman, Shaji Kumar, S. Vincent Rajkumar, Susan Slager, Asta Försti, Celine M. Vachon, Kari Hemminki
Institutions: University of South Carolina, Lund University, The University of Texas MD Anderson Cancer Center, Heidelberg University, Czech Academy of Sciences, Charles University, Czech Academy of Sciences, Institute of Experimental Medicine, University of Bonn, University of Basel, Essen University Hospital, University of Duisburg-Essen, Universität Ulm, University of Ostrava, University Hospital Ostrava, Umeå University, University of Gothenburg, Institute of Cancer Research, National Center for Tumor Diseases, Mayo Clinic, German Cancer Research Center, Hopp Children's Cancer Center Heidelberg, Deutsches Konsortium für Translationale Krebsforschung
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,590
Awards: G1016754749, G1342751976, G1493513681, ERA Chair Position for Excellent Research in Oncology, G16819465, G2906405448, G3605022155, G3682927731, G3695342494, G434337789, G5734460833, G686564698, InterLymph Consortium: interrogating pleiotropy and gene by environment interactions among hematopoietic malignancies., Mayo Clinic Comprehensive Cancer Center Support Grant
OpenAlex ID: W4223573727