Genome-wide association study identifies multiple susceptibility loci for multiple myeloma.

Genome-wide association study identifies multiple susceptibility loci for multiple myeloma.

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...

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Main Authors: Mitchell, J, Li, N, Weinhold, N, Försti, A, Ali, M, van Duin, M, Thorleifsson, G, Johnson, D, Chen, B, Halvarsson, B, Gudbjartsson, D, Kuiper, R, Stephens, O, Bertsch, U, Broderick, P, Campo, C, Einsele, H, Gregory, W, Gullberg, U, Henrion, M, Hillengass, J, Hoffmann, P, Jackson, G, Johnsson, E, Jöud, M, Kristinsson, S, Lenhoff, S, Lenive, O, Mellqvist, U, Migliorini, G, Nahi, H, Nelander, S, Nickel, J, Nöthen, M, Rafnar, T, Ross, F, da Silva Filho, M, Swaminathan, B, Thomsen, H, Turesson, I, Vangsted, A, Vogel, U, Waage, A, Walker, B, Wihlborg, A, Broyl, A, Davies, F, Thorsteinsdottir, U, Langer, C, Hansson, M, Kaiser, M, Sonneveld, P, Stefansson, K, Morgan, G, Goldschmidt, H, Hemminki, K, Nilsson, B, Houlston, R
Format: Journal article
Language:English
Published: Nature Publishing Group 2016
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Summary: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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