A polygenic risk score for multiple myeloma risk prediction

Eur J Hum Genet. 2022 Apr;30(4):474-479. doi: 10.1038/s41431-021-00986-8. Epub 2021 Nov 30.


There 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 × 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Multiple Myeloma* / diagnosis
  • Multiple Myeloma* / genetics
  • Polymorphism, Single Nucleotide
  • Risk Factors