Published online Nov 15, 2019. doi: 10.4239/wjd.v10.i11.534
Peer-review started: July 21, 2019
First decision: August 31, 2019
Revised: September 10, 2019
Accepted: October 7, 2019
Article in press: October 7, 2019
Published online: November 15, 2019
Processing time: 108 Days and 3.6 Hours
Type 1 diabetes (T1D) is described as a disease predominantly in white populations. Subtypes of the disease are also more frequent in different ethnicities. Thus, the autoimmune form of the disease is observed more frequently in Caucasian countries, whilst the idiopathic form is more frequently observed in African and Asian countries. The patients included in this study are from Northwest Colombia. This is an admixed population originated by a three ethnic contribution. This population has been described as the most European in the country, followed by the Native American ancestry, and with its least significant component being African contribution.
In this study, we looked at the genetic ancestry of a set of 200 diseased subjects from Northwest Colombia. We were interested in describing whether their global ancestry, as well as some specific genomic regions, were of which particular ancestry. Only a few of these types of studies have been reported in Latin American populations, and none have occurred in Colombia.
We aimed at describing the ancestry composition of a cohort of Colombian patients with T1D. This description included both global analysis as well as specific tests on loci/genes previously related to the disease.
We studied 200 diseased subjects from Northwest Colombia. We tested 75 admixture informative markers (AIMs) distributed through a set of previously reported genes (or chromosomal regions) associated with T1D. The disease was classified as either autoimmune or idiopathic in the study subjects. This was done by testing two disease-related auto-antibodies (AABs). If at least one such AAB was present, then the disease was classified as autoimmune. We also classified the age at onset of the disease as early (≤ 5 years) or late (> 5 years). The reference population of Colombians living in Medellin (CLM) was compared to the set of patients presented here. We applied appropriate statistical tests given the non-normality of the data obtained.
Seventy eight percent of the patients presented at least one AAB. Over two thirds (69.5%) of the subjects developed the disease after 5-years-old. There were no significant differences between genders among the affected individuals. Seventy four AIMs were successfully tested (one failed the PCR optimization). It was observed that both the diseased and CLM groups were predominantly of European ancestry (61.58 vs 62.06), followed by Native American (24.30 vs 37.10) and African ancestries (10.28 vs 10.65). In addition, specific genes such as EFR3B, IFIH1, IL7R and NRP1 displayed differential Native American or African rather than European contributions. In addition, we found that autoimmune patients displayed lower Native American ancestry than idiopathic cases.
Our study shows that diseased individuals from Northwest Colombia are predominantly of European ancestry, followed by native American and African ancestries. Also, other European contributions were found for specific genes in our study.
MHC is expected to play the strongest role in T1D susceptibility. However, this was not the observation in our study. Our results suggest that different loci effect sizes might be at play in our admix population. This is inferred from the observation of the significance strength observed for MHC ancestry compared to other loci. Therefore, it would be worth testing AIMs in this sample (expanded with extra individuals from the same region in Colombia) throughout the whole genome. This way, it would be feasible to reveal differences in local ancestry either for known or unknown loci associated with T1D in our population. This would help complete the genetic architecture of the disease, particularly for our population. In turn, this would contribute to the knowledge of the disease biology, and would also make this sample population appropriate for applying approaches such as the polygenic risk score.