Germline variants at SOHLH2 influence multiple myeloma risk

Laura Duran-Lozano, Gudmar Thorleifsson, Aitzkoa Lopez de Lapuente Portilla, Abhishek Niroula, Molly Went, Malte Thodberg, Maroulio Pertesi, Ram Ajore, Caterina Cafaro, Pall I Olason, Lilja Stefansdottir, G Bragi Walters, Gisli H Halldorsson, Ingemar Turesson, Martin F Kaiser, Niels Weinhold, Niels Abildgaard, Niels Frost Andersen, Ulf-Henrik Mellqvist, Anders WaageAnnette Juul-Vangsted, Unnur Thorsteinsdottir, Markus Hansson, Richard Houlston, Thorunn Rafnar, Kari Stefansson, Björn Nilsson

Research output: Contribution to journalArticlepeer-review


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 × 10-14). 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.

Original languageEnglish
Article number76
JournalBlood Cancer Journal
Issue number4
Publication statusPublished - 2021 Apr 19

Subject classification (UKÄ)

  • Hematology
  • Cancer and Oncology


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