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


ABSTRACT: 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.

SUBMITTER: Mitchell JS 

PROVIDER: S-EPMC4932178 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Mitchell Jonathan S JS   Li Ni N   Weinhold Niels N   Försti Asta A   Ali Mina M   van Duin Mark M   Thorleifsson Gudmar G   Johnson David C DC   Johnson David C DC   Chen Bowang B   Halvarsson Britt-Marie BM   Gudbjartsson Daniel F DF   Kuiper Rowan R   Stephens Owen W OW   Bertsch Uta U   Broderick Peter P   Campo Chiara C   Einsele Hermann H   Gregory Walter A WA   Gullberg Urban U   Henrion Marc M   Hillengass Jens J   Hoffmann Per P   Jackson Graham H GH   Johnsson Ellinor E   Jöud Magnus M   Kristinsson Sigurður Y SY   Lenhoff Stig S   Lenive Oleg O   Mellqvist Ulf-Henrik UH   Migliorini Gabriele G   Nahi Hareth H   Nelander Sven S   Nickel Jolanta J   Nöthen Markus M MM   Rafnar Thorunn T   Ross Fiona M FM   da Silva Filho Miguel Inacio MI   Swaminathan Bhairavi B   Thomsen Hauke H   Turesson Ingemar I   Vangsted Annette A   Vogel Ulla U   Waage Anders A   Walker Brian A BA   Wihlborg Anna-Karin AK   Broyl Annemiek A   Davies Faith E FE   Thorsteinsdottir Unnur U   Langer Christian C   Hansson Markus M   Kaiser Martin M   Sonneveld Pieter P   Stefansson Kari K   Morgan Gareth J GJ   Goldschmidt Hartmut H   Hemminki Kari K   Nilsson Björn B   Houlston Richard S RS  

Nature communications 20160701


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 (rs9  ...[more]

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