Germline variants at SOHLH2 influence multiple myeloma risk

Multiple myeloma (MM) is caused by the uncontrolled, clonal expansion of plasma cells. While there is epidemiological evidence for inherited susceptibility, the molecular basis remains incompletely understood. We report a genome-wide association study totalling 5,320 cases and 422,289 controls from...

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Bibliographic Details
Published in:	Blood cancer journal (New York) 2021-04, Vol.11 (4), p.76-76, Article 76
Main Authors:	Duran-Lozano, Laura, Thorleifsson, Gudmar, Lopez de Lapuente Portilla, Aitzkoa, Niroula, Abhishek, Went, Molly, Thodberg, Malte, Pertesi, Maroulio, Ajore, Ram, Cafaro, Caterina, Olason, Pall I, Stefansdottir, Lilja, Bragi Walters, G, Halldorsson, Gisli H, Turesson, Ingemar, Kaiser, Martin F, Weinhold, Niels, Abildgaard, Niels, Andersen, Niels Frost, Mellqvist, Ulf-Henrik, Waage, Anders, Juul-Vangsted, Annette, Thorsteinsdottir, Unnur, Hansson, Markus, Houlston, Richard, Rafnar, Thorunn, Stefansson, Kari, Nilsson, Björn
Format:	Article
Language:	eng
Subjects:	Aged Basic Helix-Loop-Helix Transcription Factors - genetics Cancer and Oncology Cancer och onkologi Clinical Medicine Female Gene Frequency Genetic Predisposition to Disease Genome-Wide Association Study Germ Cells - metabolism Germ-Line Mutation Hematologi Hematology Humans Klinisk medicin Linkage Disequilibrium Male Medical and Health Sciences Medicin och hälsovetenskap Multiple myeloma Multiple Myeloma - genetics Polymorphism, Single Nucleotide
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Summary:	Multiple myeloma (MM) is caused by the uncontrolled, clonal expansion of plasma cells. While there is epidemiological evidence for inherited susceptibility, the molecular basis remains incompletely understood. We report a genome-wide association study totalling 5,320 cases and 422,289 controls from four Nordic populations, and find a novel MM risk variant at SOHLH2 at 13q13.3 (risk allele frequency = 3.5%; odds ratio = 1.38; P = 2.2 × 10 ). This gene encodes a transcription factor involved in gametogenesis that is normally only weakly expressed in plasma cells. The association is represented by 14 variants in linkage disequilibrium. Among these, rs75712673 maps to a genomic region with open chromatin in plasma cells, and upregulates SOHLH2 in this cell type. Moreover, rs75712673 influences transcriptional activity in luciferase assays, and shows a chromatin looping interaction with the SOHLH2 promoter. Our work provides novel insight into MM susceptibility.
ISSN:	2044-5385 2044-5385