A polygenic risk score for multiple myeloma risk prediction

Area of Science:

• Genetics
• Epidemiology
• Oncology

Background:

• Multiple myeloma (MM) has a strong genetic component.
• Genome-wide association studies (GWAS) identified 23 MM risk loci with low individual impact.

Purpose of the Study:

• To evaluate the utility of a polygenic risk score (PRS) for MM risk stratification.
• To validate previously identified MM risk variants and their combined predictive power.

Main Methods:

• Utilized data from 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium.
• Computed weighted and unweighted PRS based on 23 single nucleotide polymorphisms (SNPs).
• Assessed the association between PRS quintiles and MM risk using odds ratios (OR) and p-values.

Main Results:

• The highest quintile of the weighted PRS showed a significant association with MM risk (OR = 3.44, P = 3.55 × 10⁻¹⁵).
• The highest quintile of the unweighted PRS also demonstrated a strong association with MM risk (OR = 3.18, P = 1.62 × 10⁻¹³).
• A PRS incorporating 23 SNPs was convincingly associated with increased MM risk.

Conclusions:

• A PRS derived from 23 validated MM risk SNPs is effective in identifying individuals at higher genetic risk for the disease.
• This PRS approach represents a foundational step towards genetic risk stratification for multiple myeloma in the general population.