The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression

Mina Ali, Ram Ajore, Anna-Karin Wihlborg, Abhishek Niroula, Bhairavi Swaminathan, Ellinor Johnsson, Owen W Stephens, Gareth Morgan, Tobias Meissner, Ingemar Turesson, Hartmut Goldschmidt, Ulf-Henrik Mellqvist, Urban Gullberg, Markus Hansson, Kari Hemminki, Hareth Nahi, Anders Waage, Niels Weinhold and Björn Nilsson ()
Additional contact information
Mina Ali: Department of Laboratory Medicine, Hematology and Transfusion Medicine
Ram Ajore: Department of Laboratory Medicine, Hematology and Transfusion Medicine
Anna-Karin Wihlborg: Department of Laboratory Medicine, Hematology and Transfusion Medicine
Abhishek Niroula: Department of Laboratory Medicine, Hematology and Transfusion Medicine
Bhairavi Swaminathan: Department of Laboratory Medicine, Hematology and Transfusion Medicine
Ellinor Johnsson: Department of Laboratory Medicine, Hematology and Transfusion Medicine
Owen W Stephens: University of Arkansas for Medical Sciences
Gareth Morgan: University of Arkansas for Medical Sciences
Tobias Meissner: Department of Molecular and Experimental Medicine, Avera Cancer Institute
Ingemar Turesson: Department of Laboratory Medicine, Hematology and Transfusion Medicine
Hartmut Goldschmidt: University of Heidelberg
Ulf-Henrik Mellqvist: South Elvsborg Hospital
Urban Gullberg: Department of Laboratory Medicine, Hematology and Transfusion Medicine
Markus Hansson: Department of Laboratory Medicine, Hematology and Transfusion Medicine
Kari Hemminki: German Cancer Research Center
Hareth Nahi: Karolinska Institutet
Anders Waage: Norwegian University of Science and Technology
Niels Weinhold: University of Arkansas for Medical Sciences
Björn Nilsson: Department of Laboratory Medicine, Hematology and Transfusion Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: Abstract Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined = 2.5 × 10−27; βcombined = −0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause–effect relationship. Our results provide mechanistic insight into MM predisposition.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-04082-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04082-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-04082-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().