Coinherited genetics of multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance

AI Clay-Gilmour; MAT Hildebrandt; EE Brown; JN Hofmann; JJ Spinelli; GG Giles; W Cozen; P Bhatti; X Wu; RG Waller; AA Belachew; DP Robinson; AD Norman; JP Sinnwell; SI Berndt; SV Rajkumar; SK Kumar; SJ Chanock; MJ Machiela; RL Milne; SL Slager; NJ Camp; E Ziv; CM Vachon

Journal article

Coinherited genetics of multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance

AI Clay-Gilmour, MAT Hildebrandt, EE Brown, JN Hofmann, JJ Spinelli, GG Giles, W Cozen, P Bhatti, X Wu, RG Waller, AA Belachew, DP Robinson, AD Norman, JP Sinnwell, SI Berndt, SV Rajkumar, SK Kumar, SJ Chanock, MJ Machiela, RL Milne Show all

Blood Advances | ELSEVIER | Published : 2020

DOI: 10.1182/bloodadvances.2020001435

Abstract

So far, 23 germline susceptibility loci have been associated with multiple myeloma (MM) risk. It is unclear whether the genetic variation associated with MM susceptibility also predisposes to its precursor, monoclonal gammopathy of undetermined significance (MGUS). Leveraging 2434 MM cases, 754 MGUS cases, and 2 independent sets of controls (2567/879),we investigated potential shared genetic susceptibility of MM and MGUS by (1) performing MM and MGUS genome-wide association studies (GWAS); (2) validating the association of a polygenic risk score (PRS) based on 23 established MM loci (MM-PRS) with risk of MM, and for the first time with MGUS; and (3) examining genetic correlation of MM and MG..

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University of Melbourne Researchers

Graham Giles Author

Roger Milne Author

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Funding Acknowledgements

This work was supported in part by the National Institutes of Health, National Cancer Institute (R25 CA092049, P30 CA016672, R01 CA134674, P30 CA042014, R01 CA186646, R21 CA155951, U54 CA118948, P30 CA13148, R25 CA47888, R01 CA235026, R01 CA107476, R01 CA168762, P50 CA186781, and the National Cancer Institute Intramural Research Program), the Leukemia Lymphoma Society (6067-09), Huntsman Cancer Institute pilot funds, the Utah Population Database, the Utah Cancer Registry, a Huntsman Cancer Center support grant, the Utah State Department of Health, the University of Utah, the Canadian Institutes of Health Research (81274), VicHealth, Cancer Council Victoria, the Australian National Health and Medical Research Council (209057, 396414, and 1074383), the Victorian Cancer Registry, the Australian Institute of Health and Welfare, the Australian National Death Index, the Australian Cancer Database, and the Mayo Clinic Cancer Center.