Type 1 diabetes loci display a variety of native American and African ancestries in diseased individuals from Northwest Colombia

Abstract

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.

A non‐codingRNASEH1gene variant associates with type 1 diabetes and interacts withHLA tagSNPsin families from Colombia

“…We analyzed 23 ancestry informative markers on chromosome 2 in 200 patients with T1D and found 0.61 of European, 0.11 of African and 0.28 of Native American ancestry. The median of the Native American ancestry tended to be higher in individuals with T1D comparing to reference population CLM 41 . This trend could explain why RNASEH1 gene is associated with T1D only in a Colombian population and not elsewhere in the world, where GWASs for this disease have been carried out.…”

“…The median of the Native American ancestry tended to be higher in individuals with T1D comparing to reference population CLM. 41 This trend could explain why RNASEH1 gene is associated with T1D only in a Colombian population and not elsewhere in the world, where GWASs for this disease have been carried out. Such GWASs did include large sample sizes, but mostly of European origin.…”

Genetic Background of Blood β-Hydroxybutyrate Acid Concentrations in Early-Lactating Holstein Dairy Cows Based on Genome-Wide Association Analyses

“…In addition, studies have suggested the involvement of the BCL2L11 gene in lipid and glucose metabolic pathways [41]. The EFR3B gene is considered a candidate gene for human type 1 diabetes [42]. On BTA 2, both the SNP BovineHD0200020100 (69,386,940 bp) and BovineHD0200025237 (88,536,618 bp) exceeded the significance threshold.…”