Genetic Ethnicity and Hypertension Epistatic Interaction Underlying Racial Disparities in US Multiple Myeloma Susceptibility

Abstract Background Multiple myeloma (MM), a malignant plasma cell disorder, exhibits pronounced racial disparities in incidence and patient outcomes. The Centers for Disease Control and Prevention (CDC) reports that MM is twice as common in Black Americans as in White Americans. Understanding these racial disparities is paramount to addressing potential healthcare biases and developing targeted interventions to ensure equitable patient care and outcomes. Methods Using the ‘All of Us’ database from the National Institute of Health, we performed a retrospective study on 413,457 participants. Of these, 1,430 were diagnosed with MM. We examined the factors contributing to racial disparities in MM risk using multivariable statistical analysis, including interaction effects. Results To comprehensively account for the multidimensional aspects of self-reported race followed by the CDC, we incorporated genetic ethnicity, demographics (age, gender), body mass index, social determinants of health (zipcode’s deprivation index, and health insurance status), and common pre-existing comorbidities (hypertension, diabetes, congestive heart failure - CHF, and chronic obstructive pulmonary disease) into our analysis. Our findings reveal that the racial disparities in health outcomes between non-Hispanic Black and non-Hispanic White individuals, as reported by the CDC, are driven by a synergistic epistatic interaction between having African as a predominant genetic ethnicity and being diagnosed or treated for hypertension (OR: 2.92, 95% CI: 1.54 to 5.57, P = 0.001). This interaction is also true for individuals whose primary genetic ancestry is Ad Mixed American (OR: 2.31, 95% CI: 1.02 to 5.2, P = 0.044). The other variables significantly associated with MM risk are having a predominant genetic ancestry of Ad Mixed American (OR: 0.41, 95% CI: 0.2 to 0.85, P = 0.017), the lack of health insurance (OR: 0.67, 95% CI: 0.48 to 0.93, P = 0.017), zipcode’s deprivation index being above the US median (OR: 1.26, 95% CI: 1.04 to 1.53, P = 0.018), being diagnosed with CHF before MM (OR: 2.06, 95% CI: 1.56 to 2.72, P < 1.e-3), being male (OR: 1.22, 95% CI: 1.02 to 1.46, P = 0.031), and being over the age of 65 (OR: 1.65, 95% CI: 1.36 to 2, P < 1.e-3). Conclusion These findings reveal a previously unknown epistatic interaction between an individual’s predominant genetic ancestry and hypertension, responsible for the CDC-reported higher risk of the African-American population for MM. In other words, hypertension serves as a surrogate marker for a genetic predisposition in individuals with a predominant African genetic ancestry. This insight could improve the screening and identification of minority individuals at risk for MM.