A new study has uncovered novel ancestry-specific genetic variants linked to multiple sclerosis, offering new insights that could reshape treatment approaches for diverse populations affected by the disease. The research is the first large-scale study to identify ancestry-specific genetic effects for MS risk.

In a comprehensive analysis of more than 7,000 individuals from self-reported Hispanic and African American backgrounds, University of Miami Miller School of Medicine researchers discovered key genetic loci linked to MS risk. The findings highlight the potential of ancestry-informed genetic studies to uncover previously unidentified risk factors for MS and to improve the precision of fine-mapping efforts across different racial and ethnic groups.

A novel genetic locus was identified on chromosome 13q14.2, specifically within African haplotypes (genetic signatures). The variant, rs3803245, is located in a region of the chromosome that is highly open to certain proteins in T-cells, suggesting this region may serve as a regulatory area in T-cells, which are crucial in MS pathology.

On chromosome 1p35.2, the research identified two distinct genetic variants linked to MS risk – one specific to Native American haplotypes and the other to European haplotypes. The Native American variant, rs145088108, significantly increases the risk of MS in Hispanics and African Americans, compared to the European variant, rs10914539.

The researchers note the variant found in Native American genetic signatures changes the structure of a protein, which might explain why it is more strongly linked to MS risk. In contrast, the variant found in European genetic signatures is in a noncoding part of the gene, making it less clear how it contributes to the disease.

The study also highlights the importance of considering gene-environment interactions in future research. While the identified variants were largely population-specific, the researchers emphasized the need to explore how environmental and lifestyle factors might interact with these and other genetic variants to influence MS risk. This is especially relevant in diverse populations with varying socioeconomic backgrounds and diets.

Researchers plan to conduct functional studies to determine the causal pathways linked to the fine-mapped variants, and to expand their cohorts to discover additional ancestry-specific variants.

The findings were presented at presented at ECTRIMS 2024.