Genomic ancestry and diversity in individuals with type 1 diabetes from Brazil and Portugal: a descriptive analysis

INTRODUCTION: Type 1 diabetes (T1D) is a chronic autoimmune disease with variable incidence worldwide,. with a higher incidence in countries of European ancestry. The present study aimed primarily to evaluate differences in genomic ancestry (GA) and genetic diversity (GD) between individuals with T1D in Brazil and Portugal compared with healthy control. Secondarily, we aimed to compare the GA and to compare the GA of individuals with T1D from different regions of Brazil with those from Portugal. METHODS: The sample included 1,698 Brazilians and 107 Portuguese individuals with T1D, whose data were analyzed using Ancestry Informative Markers (46-AIMs-Indels) to estimate the proportion of European, African, and Native American (NAM) ancestry. Allele frequencies for short (1) and long (2) alleles were estimated for all individuals. Fragment genotyping was performed by capillary electrophoresis using the ABI 3500 sequencer (Applied Biosystems). The data were analyzed using GeneMapper V.4.1 (Life Technologies, USA). STRUCTURE v2.3.3 software was used to estimate individual ancestry, with K values ranging from 2 to 5 to assess the robustness of the inferred ancestry proportions based on the HGDP-CEPH diversity panel (H952 subset) as a reference for ancestral populations. Genetic parameters were estimated using the software Arlequin v3.5.2.2 RESULTS: The results revealed a predominance of European GA in both populations, with higher European GA in Portugal and higher African and NAM GA in Brazil. A higher GD was observed in individuals with T1D from Brazil compared with those from Portugal. Non-admixed individuals with T1D from Portugal exhibited high genetic homogeneity and low genetic diversity. Individuals with T1D from the Northern Region of Brazil presented the greatest genetic differentiation compared to regional control groups.. CONCLUSION: This study identifies differences in GA and GD among individuals with T1D from Brazil and Portugal. Considering the dynamics of migrations and admixture in both countries, our data should drive future research areas related to identifying other genetic variants, such as the HLA system alleles (risk or protection) in Brazil and Portugal, which may contribute to a better understanding of the pathogenesis of the disease in both countries.