Racial and Ethnic Disease Phenotype Differences Are Driven by Genetics: Commentary

This controversy topic highlights the well-established existence of racial disparities in multiple sclerosis (MS) disease phenotype, and the importance of continued efforts towards reducing the gap in health outcomes for people living with MS. Racial and ethnic disease phenotype differences in MS include disparities in prevalence, age at onset, most frequent attack localizations, disability progression, and the functional impact of MS disability. Taking the affirmative position, Briggs contends that several genetic factors have an important influence on phenotypic variability in MS. First and foremost among these is HLA-DRB1*1501, which has been strongly associated with MS risk across studies and geographic regions. DRB1 plays a critical role in immune system function, with both B- and T-cell effects.^1,2 Interestingly, recent evidence suggests that this allele confers greater risk of MS when inherited from European “steppe” lineages, even when expressed in individuals of admixed backgrounds. DRB1*15:01 also has been associated with earlier age of onset and modest effect on MS severity.^3,4

Langer-Gould takes the opposing position, noting that race and ethnicity are social constructs. Many studies have demonstrated the importance of environmental contributors to MS risk including Epstein Barr Virus infection, tobacco smoke exposure, sunlight and vitamin D deficiency, and obesity, which, due to social and economic circumstances, vary substantially across racial and ethnic groups. Langer-Gould outlines the concept of embodiment of discrimination - that the social and environmental constructs we are born into change and influence our biology. Chronic psychosocial stress has been linked to viral shedding and more frequent EBV reactivation. ⁵ Pediatric obesity, driven by lack of access to healthy food or safe exercise spaces, is more common in Black and Hispanic communities. ⁶ Black and Hispanic people in the United States are more likely to be un- or underinsured, ⁷ which limits utilization of needed healthcare resources and can lead to worse outcomes.

We see more common ground than dissent in our colleagues’ positions. Briggs and Langer-Gould agree that while genetics can be traced to ancestral lineages, racial and ethnic groups are not defined by specific genes, but by social groupings. Moreover both Briggs and Langer-Gould acknowledge the irony in discussing the strength of genetic associations when most studies have been completed in populations overwhelmingly composed of European ancestry. A recent groundbreaking genome-wide association study identified an association between genetic variant rs10191329 in the DYSF-ZNF638 locus and earlier disability progression but data were collected only from sites in Europe, the United States and Australia; it is unknown whether this variant may distinguish disease severity in other populations. ⁸ We urgently need genetic studies with recruitment from racially and ethnically diverse people living with MS. These and other MS studies should strive to control for social determinants of health such as income, education, and the built environment, when evaluating differences across racial and ethnic populations. Finally regardless of the degree to which genetics influence MS phenotype, there is a pressing need to identify, publicize, and rectify underlying structural and social causes - including structural racism - of health disparities across racial and ethnic groups.