Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Research output: Contribution to journalJournal articleResearchpeer-review

Molly Went, Amit Sud, Asta Försti, Britt Marie Halvarsson, Niels Weinhold, Scott Kimber, Mark van Duin, Gudmar Thorleifsson, Amy Holroyd, David C. Johnson, Ni Li, Giulia Orlando, Philip J. Law, Mina Ali, Bowang Chen, Jonathan S. Mitchell, Daniel F. Gudbjartsson, Rowan Kuiper, Owen W. Stephens, Uta Bertsch & 31 more Peter Broderick, Chiara Campo, Obul R. Bandapalli, Hermann Einsele, Walter A. Gregory, Urban Gullberg, Jens Hillengass, Per Hoffmann, Graham H. Jackson, Karl Heinz Jöckel, Ellinor Johnsson, Sigurður Y. Kristinsson, Ulf Henrik Mellqvist, Hareth Nahi, Douglas Easton, Paul Pharoah, Alison Dunning, Julian Peto, Federico Canzian, Anthony Swerdlow, Rosalind A. Eeles, ZSofia S. Kote-Jarai, Kenneth Muir, Nora Pashayan, Jolanta Nickel, Markus M. Nöthen, Annette Vangsted, Niels Frost Andersen, Björn Nilsson, Børge G. Nordestgaard, The Practical Consortium

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.

Original languageEnglish
Article number3707
JournalNature Communications
Volume9
Number of pages10
ISSN2041-1723
DOIs
Publication statusPublished - 13 Sep 2018

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