SNP-Based Genetic Risk Score Modeling Suggests No Increased Genetic Susceptibility of the Roma Population to Type 2 Diabetes Mellitus

Abstract

Background: In a previous survey, an elevated fasting glucose level (FG) and/or known type 2 diabetes mellitus (T2DM) were significantly more frequent in the Roma population than in the Hungarian general population. We assessed whether the distribution of 16 single nucleotide polymorphisms (SNPs) with unequivocal effects on the development of T2DM contributes to this higher prevalence. Methods: Genetic risk scores, unweighted (GRS) and weighted (wGRS), were computed and compared between the study populations. Associations between GRSs and FG levels and T2DM status were investigated in separate and combined study populations. Results: The Hungarian general population carried a greater genetic risk for the development of T2DM (GRSGeneral = 15.38 ± 2.70 vs. GRSRoma = 14.80 ± 2.68, p < 0.001; wGRSGeneral = 1.41 ± 0.32 vs. wGRSRoma = 1.36 ± 0.31, p < 0.001). In the combined population models, GRSs and wGRSs showed significant associations with elevated FG (p < 0.001) and T2DM (p < 0.001) after adjusting for ethnicity, age, sex, body mass index (BMI), high-density Lipoprotein Cholesterol (HDL-C), and triglyceride (TG). In these models, the effect of ethnicity was relatively strong on both outcomes (FG levels: βethnicity = 0.918, p < 0.001; T2DM status: ORethnicity = 2.484, p < 0.001). Conclusions: The higher prevalence of elevated FG and/or T2DM among Roma does not seem to be directly linked to their increased genetic load but rather to their environmental/cultural attributes. Interventions targeting T2DM prevention among Roma should focus on harmful environmental exposures related to their unhealthy lifestyle.