Genome-wide association study identifies multiple susceptibility loci for multiple myeloma.
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Date
2016-07-01Author
Mitchell, JS
Li, N
Weinhold, N
Försti, A
Ali, M
van Duin, M
Thorleifsson, G
Johnson, DC
Chen, B
Halvarsson, B-M
Gudbjartsson, DF
Kuiper, R
Stephens, OW
Bertsch, U
Broderick, P
Campo, C
Einsele, H
Gregory, WA
Gullberg, U
Henrion, M
Hillengass, J
Hoffmann, P
Jackson, GH
Johnsson, E
Jöud, M
Kristinsson, SY
Lenhoff, S
Lenive, O
Mellqvist, U-H
Migliorini, G
Nahi, H
Nelander, S
Nickel, J
Nöthen, MM
Rafnar, T
Ross, FM
da Silva Filho, MI
Swaminathan, B
Thomsen, H
Turesson, I
Vangsted, A
Vogel, U
Waage, A
Walker, BA
Wihlborg, A-K
Broyl, A
Davies, FE
Thorsteinsdottir, U
Langer, C
Hansson, M
Kaiser, M
Sonneveld, P
Stefansson, K
Morgan, GJ
Goldschmidt, H
Hemminki, K
Nilsson, B
Houlston, RS
Type
Journal Article
Metadata
Show full item recordAbstract
Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10(-8)), 6q21 (rs9372120, P=9.09 × 10(-15)), 7q36.1 (rs7781265, P=9.71 × 10(-9)), 8q24.21 (rs1948915, P=4.20 × 10(-11)), 9p21.3 (rs2811710, P=1.72 × 10(-13)), 10p12.1 (rs2790457, P=1.77 × 10(-8)), 16q23.1 (rs7193541, P=5.00 × 10(-12)) and 20q13.13 (rs6066835, P=1.36 × 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
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Subject
Humans
Multiple Myeloma
Genetic Predisposition to Disease
Ubiquitin-Protein Ligases
Adaptor Proteins, Signal Transducing
Guanine Nucleotide Exchange Factors
Transcription Factors
Case-Control Studies
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p18
Genome-Wide Association Study
Polycomb Repressive Complex 2
RNA, Long Noncoding
Autophagy-Related Protein 5
Research team
Cancer Genomics
Molecular & Population Genetics
Myeloma Group
Language
eng
Date accepted
2016-05-24
License start date
2016-07
Citation
Nature communications, 2016, 7 pp. 12050 - ?
Publisher
NATURE PUBLISHING GROUP