Single-nucleotide polymorphism-based genetic risk estimate on Hungarian general and Roma population for type 2 diabetes mellitus

Werissa, Nardos
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Background: Compared with the Hungarian general population, type 2 diabetes mellitus (T2DM) and/or elevated fasting glucose level are more frequent in the Roma population. Genetic factors could be behind the difference in the prevalence between the two populations and may influence the age of onset of the disease. Objective: The aims of our study were to assess whether the distribution of 16 single nucleotide polymorphisms (SNPs) with unequivocal effects on the development of T2DM contributes to the higher prevalence of T2DM among Roma and to evaluate the impact of genetic factors on the age of onset for T2DM in addition to conventional risk factors also in the Hungarian population. Methods: A total of 1168 samples of T2DM individuals, 1783 samples from Hungarian general population and 1260 samples from segregated colonies of Roma were included in our study. Genetic risk scores, unweighted (GRS) and weighted (wGRS), were computed and compared between the study populations. Associations between GRSs and fasting glucose level and T2DM status were investigated in separate and combined study populations. For the impact of genetic factors on the age of onset for T2DM, twenty-one SNPs were tested on the case population. Twelve SNPs were chosen for the GRS analysis and the GRS was tested for validation on the Hungarian general population. 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, BMI, HDL-C, and 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). For the impact of genetic factors on the age of onset for T2DM, the GRS showed a significant association with the age of onset for T2DM (β= -0.454, p=0.001) in the case population and among T2DM patients in the HG one (β= -0.999, p=0.003) during the replication. The higher the GRS, the earlier was the T2DM onset. Conclusions: The higher prevalence of elevated FG level and/or T2DM among Roma does not appear to be directly linked to their increased genetic load but rather to their environmental/cultural attributes. Our results also suggest that there is a considerable genetic predisposition for early onset of T2DM among them. Interventions targeting T2DM prevention should focus on harmful environmental exposures related to their unhealthy lifestyle and GRS can be used as a tool for stratifying and estimating the risk of earlier onset of T2DM in addition to conventional risk factors.
Type 2 diabetes mellitus, genetic risk score, Roma, targeted intervention, single nucleotide polymorphism, age of onset for type 2 diabetes, Hungarian