Blood Cancer Journal (Apr 2021)
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 Waage,
- Annette Juul-Vangsted,
- Unnur Thorsteinsdottir,
- Markus Hansson,
- Richard Houlston,
- Thorunn Rafnar,
- Kari Stefansson,
- Björn Nilsson
Affiliations
- Laura Duran-Lozano
- Hematology and Transfusion Medicine, Department of Laboratory Medicine
- Gudmar Thorleifsson
- deCODE genetics
- Aitzkoa Lopez de Lapuente Portilla
- Hematology and Transfusion Medicine, Department of Laboratory Medicine
- Abhishek Niroula
- Hematology and Transfusion Medicine, Department of Laboratory Medicine
- Molly Went
- Division of Genetics and Epidemiology, The Institute of Cancer Research
- Malte Thodberg
- Hematology and Transfusion Medicine, Department of Laboratory Medicine
- Maroulio Pertesi
- Hematology and Transfusion Medicine, Department of Laboratory Medicine
- Ram Ajore
- Hematology and Transfusion Medicine, Department of Laboratory Medicine
- Caterina Cafaro
- Hematology and Transfusion Medicine, Department of Laboratory Medicine
- Pall I. Olason
- deCODE genetics
- Lilja Stefansdottir
- deCODE genetics
- G. Bragi Walters
- deCODE genetics
- Gisli H. Halldorsson
- deCODE genetics
- Ingemar Turesson
- Hematology Clinic, Lund University Hospital
- Martin F. Kaiser
- Division of Genetics and Epidemiology, The Institute of Cancer Research
- Niels Weinhold
- Department of Internal Medicine V, University Hospital of Heidelberg
- Niels Abildgaard
- Hematology Research Unit, Department of Clinical Research, University of Southern Denmark and Department of Hematology, Odense University Hospital
- Niels Frost Andersen
- Department of Haematology, Aarhus University Hospital
- Ulf-Henrik Mellqvist
- Södra Älvsborgs Sjukhus Borås
- Anders Waage
- Institute of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Department of Hematology, and Biobank1, St Olavs hospital
- Annette Juul-Vangsted
- Department of Haematology, University Hospital of Copenhagen at Rigshospitalet
- Unnur Thorsteinsdottir
- deCODE genetics
- Markus Hansson
- Hematology and Transfusion Medicine, Department of Laboratory Medicine
- Richard Houlston
- Division of Genetics and Epidemiology, The Institute of Cancer Research
- Thorunn Rafnar
- deCODE genetics
- Kari Stefansson
- deCODE genetics
- Björn Nilsson
- Hematology and Transfusion Medicine, Department of Laboratory Medicine
- DOI
- https://doi.org/10.1038/s41408-021-00468-6
- Journal volume & issue
-
Vol. 11,
no. 4
pp. 1 – 8
Abstract
Abstract 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.
