BACKGROUNDThe global epidemiology of type 1 diabetes (T1D) is not yet well known, as no precise data are available from many countries. T1D is, however, characterized by an important variation in incidences among countries and a dramatic increase of these incidences during the last decades, predominantly in younger children. In the United States and Europe, the increase has been associated with the gross domestic product (GDP) per capita. In our previous systematic review, geographical variation of incidence was correlated with socio-economic factors.AIMTo investigate variation in the incidence of T1D in age categories and search to what extent these variations correlated with the GDP per capita.METHODSA systematic review was performed to retrieve information about the global incidence of T1D among those younger than 14 years of age. The study was carried out according to the PRISMA recommendations. For the analysis, the incidence was organized in the periods: 1975-1999 and 2000-2017. We searched the incidence of T1D in the age-groups 0-4, 5-9 and 10-14. We compared the incidences in countries for which information was available for the two periods. We obtained the GDP from the World Bank. We analysed the relationship between the incidence of T1D with the GDP in countries reporting data at the national level.RESULTSWe retrieved information for 84 out of 194 countries around the world. We found a wide geographic variation in the incidence of T1D and a worldwide increase during the two periods. The largest contribution to this increase was observed in the youngest group of children with T1D, with a relative increase of almost double when comparing the two periods (P value = 2.5 × e-5). Twenty-six countries had information on the incidence of T1D at the national level for the two periods. There was a positive correlation between GDP and the incidence of T1D in both periods (Spearman correlation = 0.52 from 1975-1999 and Spearman correlation = 0.53 from 2000-2017).CONCLUSIONThe incidence increase was higher in the youngest group (0-4 years of age), and the highest incidences of T1D were found in wealthier countries.

BACKGROUNDType 1 diabetes (T1D) is a complex disease with a higher incidence in Europeans than other populations. The Colombians Living in Medellin (CLM) is admixed with ancestry contributions from Europeans, Native Americans (NAT) and Africans (AFR).AIMOur aim was to analyze the genetic admixture component at candidate T1D loci in Colombian individuals with the disease.METHODSSeventy-four ancestry informative markers (AIMs), which tagged 41 T1D candidate loci/genes, were tested by studying a cohort of 200 Northwest Colombia diseased individuals. T1D status was classified by testing for glutamic acid decarboxylase (GAD-65 kDa) and protein tyrosine-like antigen-2 auto-antibodies in serum samples. Candidate loci/genes included HLA, INS, PTPN22, CTLA4, IL2RA, SUMO4, CLEC16A, IFIH1, EFR3B, IL7R, NRP1 and RNASEH1, amongst others. The 1,000 genome database was used to analyze data from 94 individuals corresponding to the reference CLM. As the data did not comply with a normal distribution, medians were compared between groups using the Mann-Whitney U-test.RESULTSBoth T1D patients and individuals from CLM displayed mainly European ancestry (61.58 vs 62.06) followed by Native American (27.34 vs 27.46) and to a lesser extent the AFR ancestry (10.28 vs 10.65) components. However, compared to CLM, ancestry of T1D patients displayed a decrease of NAT ancestry at gene EFR3B (24.30 vs 37.10) and an increase at genes IFIH1 (32.07 vs 14.99) and IL7R (52.18 vs 39.18). Also, for gene NRP1 (36.67 vs 0.003), we observed a non-AFR contribution (attributed to NAT). Autoimmune patients (positive for any of two auto-antibodies) displayed lower NAT ancestry than idiopathic patients at the MHC region (20.36 vs 31.88). Also, late onset patients presented with greater AFR ancestry than early onset patients at gene IL7R (19.96 vs 6.17). An association analysis showed that, even after adjusting for admixture, an association exists for at least seven such AIMs, with the strongest findings on chromosomes 5 and 10 (gene IL7R, P = 5.56 × 10-6 and gene NRP1, P = 8.70 × 10-19, respectively).CONCLUSIONAlthough Colombian T1D patients have globally presented with higher European admixture, specific T1D loci have displayed varying levels of Native American and AFR ancestries in diseased individuals.

La diabetes mellitus tipo 1 (DM1) es una enfermedad autoinmune crónica de aparición en la infancia y el adulto joven. El subtipo autoinmune (DM1A) es más frecuente en personas con ancestría europea, mientras que el subtipo idiopático (DM1B) es más común en poblaciones de ancestría africana y asiática. Acá presentamos las características demográficas de un grupo de familias “paisas” con al menos un hijo con DM1. Se incluyó una muestra de 200 familias nucleares a las cuales se les aplicó una encuesta que preguntó aspectos generales como género, edad de diagnóstico, origen de los padres, abuelos y bisabuelos. Además se obtuvo la información sobre los autoanticuerpos anti-INS, anti-GAD, anti-ICAs y anti-TPO en 100 de los niños con diagnóstico de DM1. Se encontró que la edad media de diagnóstico fue 7,4 años. El 55% de las familias provenían del oriente antioqueño y el Valle de Aburrá. El 8,4% de los niños tenían un hermano con DM1. Además se pudo determinar que el 80,1% de los niños padecen DM1A, pues estos presentaban al menos un autoanticuerpo. Los resultados sobre autoinmunidad y la edad de diagnóstico permiten asimilar esta muestra con poblaciones europeas, en vez de africanos o asiáticos.  Abstract Type 1 diabetes (T1D) is a chronic autoimmune disease with onset at infancy and early adulthood. The autoimmune subtype (T1DA) is the most frequent in people with European ancestry, whilst the idiopathic subtype (T1DB) is the commonest in populations of African or Asian ancestry. Here we present the demographic features of a set of “paisa” families which had al least one child with T1D. Two hundred nuclear families were included. An instrument asking for general information such as gender, age at diagnosis, origin of their parents, grandparents and great- grandparents was applied. In addition, auto-antibodies data for INS, GAD, IA2 and TPO were obtained in a sub-set of 100 patients. The age at diagnosis was 7,4 years. 55% of the families came from “Oriente”, “Norte” and “Suroeste” sub-regions. 8,4% of the children had one sib with the disease. Besides, it could be determined that 80,1% of the tested sample had T1DA, since they presented at least one type 1 diabetes related auto-antibody. Our results on autoimmunity and age at diagnosis let us assimilate this sample with European populations, rather than Africans or Asians.

La respuesta a la selección natural en caracteres cuantitativos en una población natural depende de la magnitud de variabilidad genética y las correlaciones genéticas en los rasgos, y estos parámetros genéticos pueden diferir entre categorías de rasgos. En este estudio se caracterizaron los patrones de varianza y covarianza fenotípica y se realizaron estimaciones de heredabilidad (h2) y correlaciones genéticas de rasgos morfológicos y fisiológicos en una población de Zamia obliqua (Zamiaceae: Cycadales). Se probaron las hipótesis de que la varianza y la heredabilidad de rasgos morfológicos son mayores que las de rasgos fisiológicos, y que las correlaciones fenotípicas y genéticas son mayores dentro que entre las categorías de rasgos. Los valores de varianza fenotípica fueron mayores en los rasgos fisiológicos comparados con los caracteres morfológicos. Los estimativos de heredabilidad sugieren que los caracteres morfológicos presentan mayor varianza genética que los rasgos fisiológicos. Por otro lado, no se obtuvieron correlaciones genéticas significativas entre los rasgos. Sin embargo, las correlaciones fenotípicas muestran mayor correlación dentro de los caracteres morfológicos que dentro de los fisiológicos o entre rasgos morfológicos y fisiológicos. Estas estimaciones de parámetros genéticos permiten construir hipótesis sobre la evolución de caracteres fenotípicos en poblaciones naturales, y son aportes importantes al estudio de la ecología evolutiva de especies no modelo y sus poblaciones en hábitats naturales.

Objectives: RNASEH1 gene has recently been associated with type 1 diabetes (T1D) in Colombia. The purpose of this study was to fine mapping the putative functional variant in RNASEH1 and testing its interaction with HLA tagSNPs. Methods: Two-hundred nuclear families with T1D were included in this study. Probands were tested for GAD65 and IA-2 autoantibodies. Genotyping was performed using 20 coding tagSNPs uncovered through Sanger sequencing (N = 96), in addition to 23 tagSNPs chosen from 1000genomes to cover the extent of the gene region. Also, 45 tagSNPs for classic HLA alleles associated with T1D were also genotyped. The transmission disequilibrium test (TDT) was used to test for association and a multiple testing correction was made using permutation. Interaction between RNASEH1 variants and HLA was evaluated by means of the M-TDT test. Results: We identified 20 variants (15 were novel) in the 96 patients sequenced. None of these variants were in linkage disequilibrium. In total, 43 RNASEH1 variants were genotyped in the 200 families. Association between T1D and rs7607888 was identified (P = .002). Haplotype analysis involving rs7607888 variant revealed even stronger association with T1D (most significative P = .0003). HLA tagSNPs displayed stronger associations (OR = 6.39, 95% CI = 4.33-9.44, P-value = 9.74E-28). Finally, we found several statistically significant interactions of HLA variants with rs7607888 (P-value ranged from 8.77E-04 to 5.33E-12). Conclusion: Our results verify the association of rs7607888 in RNASEH1 gene with T1D. It is also shown in the interaction between RNASEH1 and HLA for conveying risk to T1D in Northwest Colombia. Work is underway aiming to identify the actual classic HLA alleles associated with the tagSNPs tested here.