Fine-Scale Genetic Structure in the United Arab Emirates Reflects Endogamous and Consanguineous Culture, Population History, and Geography.

The indigenous population of the United Arab Emirates (UAE) has a unique demographic and cultural history. Its tradition of endogamy and consanguinity is expected to produce genetic homogeneity and partitioning of gene pools while population movements and intercontinental trade are likely to have contributed to genetic diversity. Emiratis and neighboring populations of the Middle East have been underrepresented in the population genetics literature with few studies covering the broader genetic history of the Arabian Peninsula. Here, we genotyped 1,198 individuals from the seven Emirates using 1.7 million markers and by employing haplotype-based algorithms and admixture analyses, we reveal the fine-scale genetic structure of the Emirati population. Shared ancestry and gene flow with neighboring populations display their unique geographic position while increased intra- versus inter-Emirati kinship and sharing of uniparental haplogroups, reflect the endogamous and consanguineous cultural traditions of the Emirates and their tribes.

Monogenic diabetes variants in Emirati women with gestational diabetes are associated with risk of non-autoimmune diabetes within 5 years after pregnancy.

Aims: To investigate the prevalence of pathogenic variants in monogenic diabetes genes in Emirati women with gestational diabetes (GDM) and examine the risk of developing hyperglycemia during follow-up in carriers and non-carriers. Methods: Female patients with GDM (n = 370) were identified. Selected monogenic diabetes genes, GCK, HNF1A, HNF4A, HNF1B, INS, ABCC8 and KCNJ1I, were examined by sequencing and identified variants were classified. Anthropometrics and subsequent diagnosis of diabetes were extracted from hospital records. Median follow-up time was 6-years. Results: A total of 34 variants were detected. Seven women (2%) were carriers of pathogenic variants in GCK, HNF1A, INS, ABCC8 or KCNJ11. A significantly larger fraction of women carrying pathogenic variants were diagnosed with any form of hyperglycemia or diabetes postpartum (risk ratio = 1.8 (1.1-2.9), p = 0.02) or 2.5 (1.3-4.8; p = 0.009), respectively) and they had a shorter disease-free period after GDM compared to women without such variants. There were no significant associations between carrying pathogenic variants and anthropometric measures or C-peptide. Conclusions: Pathogenic variants were found in known monogenic diabetes genes in two percent of Emirati women with GDM, allowing for precision medicine utilisation in these women both during and outside pregnancy. Carriers were at an increased risk of being diagnosed with hyperglycemia or type 2 diabetes mellitus within 5 years after pregnancy.