A polygenic risk score for multiple myeloma risk prediction

• Published in: European journal of human genetics : EJHG 2022-04, Vol.30 (4), p.474-479
• Main Authors: Canzian, Federico, Piredda, Chiara, Macauda, Angelica, Zawirska, Daria, Andersen, Niels Frost, Nagler, Arnon, Zaucha, Jan Maciej, Mazur, Grzegorz, Dumontet, Charles, Wątek, Marzena, Jamroziak, Krzysztof, Sainz, Juan, Várkonyi, Judit, Butrym, Aleksandra, Beider, Katia, Abildgaard, Niels, Lesueur, Fabienne, Dudziński, Marek, Vangsted, Annette Juul, Pelosini, Matteo, Subocz, Edyta, Petrini, Mario, Buda, Gabriele, Raźny, Małgorzata, Gemignani, Federica, Marques, Herlander, Orciuolo, Enrico, Kadar, Katalin, Jurczyszyn, Artur, Druzd-Sitek, Agnieszka, Vogel, Ulla, Andersen, Vibeke, Reis, Rui Manuel, Suska, Anna, Avet-Loiseau, Hervé, Kruszewski, Marcin, Tomczak, Waldemar, Rymko, Marcin, Minvielle, Stephane, Campa, Daniele
• Format: Article
• Language: English
• Subjects: Cancer; Epidemiology; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Humans; Life Sciences; Multiple myeloma; Multiple Myeloma - diagnosis; Multiple Myeloma - genetics; Polymorphism, Single Nucleotide; Risk Factors; Single-nucleotide polymorphism
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/s41431-021-00986-8

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 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 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.