Reaching the full potential of precision medicine depends on the quality of personalized genome interpretation. In order to facilitate precision medicine in regions of the Middle East and North Africa (MENA), a population-specific genome for the indigenous Arab population of Qatar (QTRG) was constructed by incorporating allele frequency data from sequencing of 1,161 Qataris, representing 0.4% of the population. A total of 20.9 million single nucleotide polymorphisms (SNPs) and 3.1 million indels were observed in Qatar, including an average of 1.79% novel variants per individual genome. Replacement of the GRCh37 standard reference with QTRG in a best practices genome analysis workflow resulted in an average of 7* deeper coverage depth (an improvement of 23%) and 756,671 fewer variants on average, a reduction of 16% that is attributed to common Qatari alleles being present in QTRG. The benefit for using QTRG varies across ancestries, a factor that should be taken into consideration when selecting an appropriate reference for analysis.

Diabetes is a significant health problem worldwide, and its association with cardiovascular disease (CVD) was reported in several studies. Hyperglycemia and insulin resistance seen in diabetes and prediabetes lead to an increase in reactive oxygen species, which triggers intracellular molecular signaling. The resulting prothrombotic state and increase in inflammatory mediators expedite atherosclerotic changes and the development of macrovascular complications. Individuals with diabetes or prediabetes have a higher risk of developing myocardial infarction, stroke, and peripheral artery disease. However, no significant difference in cardiovascular morbidity has been observed with tight glycemic control despite a reduction in some CVD outcomes, and the risk of adverse outcomes such as hypoglycemia was increased. Recently, some GLP-1 receptor agonists and SGLT-2 inhibitors have been shown to reduce cardiovascular events and mortality. In this review we give an overview of the risk and pathogenesis of cardiovascular disease among diabetic and prediabetic patients, as well as the implication of recent changes in diabetes management.

An open question in the history of human migration is the identity of the earliest Eurasian populations that have left contemporary descendants. The Arabian Peninsula was the initial site of the out-of-Africa migrations that occurred between 125,000 and 60,000 yr ago, leading to the hypothesis that the first Eurasian populations were established on the Peninsula and that contemporary indigenous Arabs are direct descendants of these ancient peoples. To assess this hypothesis, we sequenced the entire genomes of 104 unrelated natives of the Arabian Peninsula at high coverage, including 56 of indigenous Arab ancestry. The indigenous Arab genomes defined a cluster distinct from other ancestral groups, and these genomes showed clear hallmarks of an ancient out-of-Africa bottleneck. Similar to other Middle Eastern populations, the indigenous Arabs had higher levels of Neanderthal admixture compared to Africans but had lower levels than Europeans and Asians. These levels of Neanderthal admixture are consistent with an early divergence of Arab ancestors after the out-of-Africa bottleneck but before the major Neanderthal admixture events in Europe and other regions of Eurasia. When compared to worldwide populations sampled in the 1000 Genomes Project, although the indigenous Arabs had a signal of admixture with Europeans, they clustered in a basal, outgroup position to all 1000 Genomes non-Africans when considering pairwise similarity across the entire genome. These results place indigenous Arabs as the most distant relatives of all other contemporary non-Africans and identify these people as direct descendants of the first Eurasian populations established by the out-of-Africa migrations.

Exome sequencing of families of related individuals has been highly successful in identifying genetic polymorphisms responsible for Mendelian disorders. Here, we demonstrate the value of the reverse approach, where we use exome sequencing of a sample of unrelated individuals to analyze allele frequencies of known causal mutations for Mendelian diseases. We sequenced the exomes of 100 individuals representing the three major genetic subgroups of the Qatari population (Q1 Bedouin, Q2 Persian-South Asian, Q3 African) and identified 37 variants in 33 genes with effects on 36 clinically significant Mendelian diseases. These include variants not present in 1000 Genomes and variants at high frequency when compared to 1000 Genomes populations. Several of these Mendelian variants were only segregating in one Qatari subpopulation, where the observed subpopulation specificity trends were confirmed in an independent population of 386 Qataris. Pre-marital genetic screening in Qatar tests for only 4 out of the 37, such that this study provides a set of Mendelian disease variants with potential impact on the epidemiological profile of the population that could be incorporated into the testing program if further experimental and clinical characterization confirms high penetrance.

Aims Much of the diabetes burden is caused by its complications. This cross-sectional study aimed to determine the prevalence and risk factors for diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) in a high-risk population. Methods We collected information via a structured questionnaire and directly from the patient's record on 1034 adult type 2 diabetic patients who were attending outpatient clinics in Qatar. Results The mean age of the patients was 55 ± 10 years, and the mean duration of diabetes was 12.4 ± 8.9 years. Forty-five percent had one or more microvascular complications. Shared risk factors for multiplicity and for individual complications included family history, severity and duration of diabetes, and hypertension, but some risk factors were specific for individual microvascular complications. Early age at onset of diabetes was strongly associated with multiplicity of complications (P = 0.0003). Conclusions About half the diabetics in this high-risk population had one or more microvascular complications. Several well-established risk factors were associated with multiplicity and individual microvascular complications, but each separate microvascular complication was linked to a somewhat different constellation of risk factors.