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Article Dans Une Revue European Journal of Human Genetics Année : 2021

A polygenic risk score for multiple myeloma risk prediction

1 GEP / DKFZ - Genomic Epidemiology Group [Heidelberg, Germany]
2 University of Pisa - Università di Pisa
3 SUK - University Hospital of Cracow/Szpital Uniwersytecki w Krakowie [Poland]
4 Aarhus University Hospital
5 Chaim Sheba Medical Center
6 SH - Sea Hospital [Gdynia, Poland]
7 Wrocław Medical University
8 HCL - Hospices Civils de Lyon
9 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
10 Holycross Cancer Center of Kelce, Hematology Clinic, Kielce
11 IHTM - Institute of Hematology and Transfusion Medicine [Warsaw, Poland]
12 GENYO - Centre for Genomics and Oncological Research Pfizer [Granada, Spain]
13 HUVN - Hospital Universitario Virgen de las Nieves [Granada, Spain]
14 Semmelweis University [Budapest]
15 OUH - Odense University Hospital
16 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
17 TH1 - Teaching Hospital No 1 [Rzeszów, Poland]
18 UCPH - University of Copenhagen = Københavns Universitet
19 MIM - Military Institute of Medicine [Warsaw, Poland]
20 RSH - Rydygier Specialistic Hospital [Cracow, Poland]
21 Universidade do Minho = University of Minho [Braga]
22 UJ - Uniwersytet Jagielloński w Krakowie = Jagiellonian University
23 MCMCC - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
24 NRCWE - The National Research Center for Work Environment [Copenhagen, Denmark]
25 SDU - University of Southern Denmark
26 AL - ICVS/3B's - PT Government Associate Laboratory [Braga/Guimarães, Portugal]
27 BCH - Barretos Cancer Hospital [São Paulo, Brazil]
28 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
29 UHB - University Hospital Bydgoszcz [Bydgoszcz, Poland]
30 Medical University of Lublin
31 NCTH - N. Copernicus Town Hospital [Torun, Poland]
32 CRCINA-ÉQUIPE 11 - Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression
Arnon Nagler

Résumé

There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genomewide 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 × 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 × 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.

Domaines

Cancer
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Origine : Publication financée par une institution

Dates et versions

inserm-03480934 , version 1 (15-12-2021)

Identifiants

Citer

Federico Canzian, Chiara Piredda, Angelica Macauda, Daria Zawirska, Niels Frost Andersen, et al.. A polygenic risk score for multiple myeloma risk prediction. European Journal of Human Genetics, 2021, Online ahead of print. ⟨10.1038/s41431-021-00986-8⟩. ⟨inserm-03480934⟩
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