A polygenic risk score for multiple myeloma risk prediction
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Federico Canzian
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- Function : Correspondent author
- PersonId : 908773
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Arnon Nagler
- Function : Author
- PersonId : 777286
- ORCID : 0000-0002-0763-1265
Fabienne Lesueur
- Function : Author
- PersonId : 766610
- ORCID : 0000-0001-7404-4549
- IdRef : 165329939
Federica Gemignani
- Function : Author
- PersonId : 771791
- ORCID : 0000-0003-1297-0701
Marcin Kruszewski
- Function : Author
- PersonId : 847006
Stephane Minvielle
- Function : Author
- PersonId : 738362
- IdHAL : stephane-minvielle
- ORCID : 0000-0003-1389-312X
- IdRef : 032987552
Abstract
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.
Origin : Publication funded by an institution