Canzian, FedericoPiredda, ChiaraMacauda, AngelicaZawirska, DariaAndersen, Niels FrostNagler, ArnonZaucha, Jan MaciejMazur, GrzegorzDumontet, CharlesWatek, MarzenaJamroziak, KrzysztofSainz, JuanVarkonyi, JuditButrym, AleksandraBeider, KatiaAbildgaard, NielsLesueur, FabienneDudzinski, MarekVangsted, Annette JuulPelosini, MatteoSubocz, EdytaPetrini, MarioBuda, GabrieleRazny, MalgorzataGemignani, FedericaMarques, HerlanderOrciuolo, EnricoKadar, KatalinJurczyszyn, ArturDruzd-Sitek, AgnieszkaVogel, UllaAndersen, VibekeReis, Rui ManuelSuska, AnnaAvet-Loiseau, HerveKruszewski, MarcinTomczak, WaldemarRymko, MarcinMinvielle, StephaneCampa, Daniele2025-01-072025-01-072021-11-301018-4813https://hdl.handle.net/10668/26366There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53-4.69, p = 3.55 x 10(-15) for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34-4.33, p = 1.62 x 10(-13) for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Monoclonal gammopathyStratificationPolymorphismsEpidemiologyresearch article34845334open access10.1038/s41431-021-00986-81476-5438https://www.nature.com/articles/s41431-021-00986-8.pdf723492300001