Results: As of August, a total of 30,133 individuals were screened, including 15,500 high-risk participants. The median age at sample was 56 years (IQR:44-64), 60% were females, 28% Black/AA, and 24% Non-Black with FH-HM.

The overall prevalence of MGUS was 12.6% (n= 3,793; 95CI 12.2 - 13%), with LC-MGUS accounting for 1.6%. In high-risk populations aged ≥50 years, MGUS prevalence was higher in Black/AA individuals (17.8%) compared to Non-Black individuals with FH-HM (14.8%, p<0.001). Multivariable regression identified age (per 10-year increase) as the strongest predictor of MGUS, followed by Black race (OR 1.29, 95CI 1.06–1.57; p=0.01), male sex (OR 1.22, 95CI 1.09–1.36; p<0.001), and FH-HM (OR 1.16, 95CI 1.003- 1.33; p=0.046). BMI (per 5-unit change) and sample origin were not significant predictors. Subgroup analysis revealed that within individuals with FH-HM, race remained significantly associated with MGUS prevalence (OR 1.27, 95CI 1.12-1.44; p<0.001), while FH-HM was not a factor among self-identified Black individuals. Additionally, BMI demonstrated a unique association with MGUS prevalence in Black individuals (OR 1.12, 95CI 1.02-1.21; p=0.008), while age and sex remained significant predictors across groups.

Examining genetic ancestry in the multivariable model showed significant association between African ancestry and MGUS (OR 1.21; 95CI 1.07-1.38; p=0.003), suggesting a genetic contribution to the observed racial disparity. After adjusting for age and sex, no significant difference in MGUS prevalence was found between Black/AA individuals residing in South Africa and those residing in the US.

When comparing isotypes across groups, IgM MGUS prevalence was significantly lower in Black/AAs compared to the non-high-risk group (6% vs.17%; p<0.001), while IgG MGUS and IgA MGUS were more common (77% vs. 72%, p=0.016 and 17% vs. 11%, p<0.001). Among Non-Black individuals, only IgA MGUS prevalence was significantly higher in those with a FH-HM compared to those without (16% vs. 11%, p=0.002). In addition, significant differences in concentration were observed for IgM and IgG between risk groups, with a higher concentration of IgG MGUS in Black/AA compared to Non-Black risk groups (p<0.001).

Conclusion:

As efforts grow to evaluate population-level screening, this study in a racially diverse population refines risk stratification, identifying subgroups most likely to benefit while minimizing false positives. The higher prevalence in individuals of Black race and African ancestry, along with distinct age-related patterns, provides a foundation to assess the implications of targeted screening strategies and inform future screening guidelines.