Germline variants at SOHLH2 influence multiple myeloma risk.

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ICR Authors

Went, Molly
 Kaiser, Martin
 Houlston, Richard

Authors

Duran-Lozano, L
Thorleifsson, G
Lopez de Lapuente Portilla, A
Niroula, A
Went, M
Thodberg, M
Pertesi, M
Ajore, R
Cafaro, C
Olason, PI
Stefansdottir, L
Bragi Walters, G
Halldorsson, GH
Turesson, I
Kaiser, MF
Weinhold, N
Abildgaard, N
Andersen, NF
Mellqvist, U-H
Waage, A
Juul-Vangsted, A
Thorsteinsdottir, U
Hansson, M
Houlston, R
Rafnar, T
Stefansson, K
Nilsson, B

Document Type

Journal Article

Date

2021-04-19

Date Accepted

2021-03-31

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.

Citation

Blood cancer journal, 2021, 11 (4), pp. 76 - ?

DOI

10.1038/s41408-021-00468-6

URI

https://repository.icr.ac.uk/handle/internal/4634

Rights

https://creativecommons.org/licenses/by/4.0

Source Title

Publisher

SPRINGERNATURE

ISSN

2044-5385

eISSN

2044-5385

Collections

Genetics and Epidemiology
Cancer Biology

Research Team

Cancer Genomics
Myeloma Group
Cancer Genomics
Myeloma Group

Notes