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Germline variants at SOHLH2 influence multiple myeloma risk

Duran-Lozano, Laura LU ; Thorleifsson, Gudmar ; Lopez de Lapuente Portilla, Aitzkoa LU ; Niroula, Abhishek LU ; Went, Molly ; Thodberg, Malte LU ; Pertesi, Maroulio LU ; Ajore, Ram LU ; Cafaro, Caterina LU and Olason, Pall I , et al. (2021) In Blood Cancer Journal 11(4).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood Cancer Journal
volume
11
issue
4
article number
76
publisher
Nature Publishing Group
external identifiers
  • pmid:33875642
  • scopus:85104540884
ISSN
2044-5385
DOI
10.1038/s41408-021-00468-6
language
English
LU publication?
yes
id
d5f905c0-5220-489e-ad23-c8d9eacbca15
date added to LUP
2021-04-21 18:32:11
date last changed
2024-03-08 11:29:59
@article{d5f905c0-5220-489e-ad23-c8d9eacbca15,
  abstract     = {{<p>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.</p>}},
  author       = {{Duran-Lozano, Laura and Thorleifsson, Gudmar and Lopez de Lapuente Portilla, Aitzkoa and Niroula, Abhishek and Went, Molly and Thodberg, Malte and Pertesi, Maroulio and Ajore, Ram and Cafaro, Caterina and Olason, Pall I and Stefansdottir, Lilja and Bragi Walters, G and Halldorsson, Gisli H and Turesson, Ingemar and Kaiser, Martin F and Weinhold, Niels and Abildgaard, Niels and Andersen, Niels Frost and Mellqvist, Ulf-Henrik and Waage, Anders and Juul-Vangsted, Annette and Thorsteinsdottir, Unnur and Hansson, Markus and Houlston, Richard and Rafnar, Thorunn and Stefansson, Kari and Nilsson, Björn}},
  issn         = {{2044-5385}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Blood Cancer Journal}},
  title        = {{Germline variants at SOHLH2 influence multiple myeloma risk}},
  url          = {{http://dx.doi.org/10.1038/s41408-021-00468-6}},
  doi          = {{10.1038/s41408-021-00468-6}},
  volume       = {{11}},
  year         = {{2021}},
}